Strategies for ABO-incompatible liver transplantation / 器官移植

With rapid development of organ transplantation, the issue of global organ shortage has become increasingly prominent. At present, liver transplantation is the most effective treatment for end-stage liver disease. Nevertheless, the shortage of donors has been a key problem restricting the development of liver transplantation. China is a country with a larger number of hepatitis B, and the shortage of donor liver is particularly significant. Many critically ill patients often lose the best opportunity or even die because they cannot obtain a matched donor liver in time. As a strategy to expand the donor pool, ABO-incompatible (ABOi) liver transplantation offers new options for patients who are waiting for matched donors. However, ABOi liver transplantation is highly controversial due to higher risk of complications, such as severe infection, antibody-mediated rejection (AMR), biliary complications, thrombotic microangiopathy, and acute kidney injury, etc. In this article, research progress in preoperative, intraoperative and postoperative strategies of ABOi liver transplantation was reviewed, aiming to provide reference for clinical application and research of ABOi liver transplantation.

Research progress of B lymphocytes in non-infectious uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

Non-infectious uveitis, an autoimmune disease that can cause severe visual impairment, can be difficult to treat. According to the prevailing hypothesis, the immune-mediated imbalance that contributes to non-infectious uveitis is primarily driven by CD4+T cells. However, recent research has shown that B cells also play a significant role in this process, participating in various ways such as antibody production, antigen presentation, and cytokine secretion in both human uveitis and experimental autoimmune uveitis models. Therapies targeting B cells have been used extensively in various autoimmune diseases. Rituximab, a B-cell inhibitor, is effective in treating noninfectious uveitis that is unresponsive to conventional corticosteroid and immunosuppressive therapy. This paper provides an overview of the involvement of B cells in non-infectious uveitis and their potential use in cellular therapies, aiming to further investigate the mechanisms and develop more effective strategies for prevention and treatment.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center / Terapia com Rituximabe para síndrome nefrótica idiopática de início na infância: experiência de um centro terciário português

ABSTRACT Introduction: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. Method: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Results: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Conclusion: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [0,29 (0,15-0,67) >vs [0,10 (0,07-0,13); p = 0,001], [0,12 (0,05-0,22); p = 0,005] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.

Hipogamaglobulinemia e rituximabe: relato de casos / Hypogammaglobulinemia and rituximab: case reports

Secondary immunodeficiency can result from neoplasms, infections, or immunosuppressive therapy. Rituximab (RTX) is an anti-CD20 antibody that depletes B lymphocytes and can induce symptomatic hypogammaglobulinemia. We report 3 cases of symptomatic hypogammaglobulinemia associated with the use of RTX. In patient 1 with rheumatoid arthritis, RTX induced low levels of immunoglobulins and recurrent airway infections. RTX discontinuation led to a normalization of the humoral immune response. Patients 2 and 3, treated with RTX for non-Hodgkin lymphoma and systemic lupus erythematosus, respectively, developed persistent secondary hypogammaglobulinemia requiring immunoglobulin replacement therapy for years. After RTX discontinuation, patients may experience rapid recovery of humoral function or remain with low serum immunoglobulin levels for extended periods. With the increasing use of therapies targeting components of the immune system, a high degree of clinical suspicion for the development of secondary immunodeficiency may minimize the morbidity and mortality associated with these therapies.

As imunodeficiências secundárias podem ser uma consequência de neoplasias, infecções ou tratamentos imunossupressores. O rituximabe (RTX) é um anticorpo anti-CD20 que depleta os linfócitos B e pode induzir uma hipogamaglobulinemia sintomática. Aqui, relatamos três casos de hipogamaglobulinemia sintomática associada ao uso de RTX. Na primeira paciente com artrite reumatoide, o RTX induziu a baixos níveis de imunoglobulinas associadas a infecções de vias aéreas de repetição. Após a suspensão do RTX, houve normalização da resposta imune humoral. Os outros dois casos, com o uso de RTX para tratamento de linfoma não-Hodgkin e lúpus eritematoso sistêmico, respectivamente, as pacientes evoluíram com hipogamaglobulinemia secundária persistente, com necessidade de reposição de imunoglobulina por vários anos. Pacientes tratados com RTX podem apresentar, após a sua suspensão, uma recuperação rápida da função humoral ou permanecerem com baixos níveis séricos de imunoglobulinas por longos períodos. Com o crescente uso dos tratamentos direcionados para componentes do sistema imunológico, um alto grau de suspeição clínica para o aparecimento de imunodeficiências secundárias pode minimizar a morbimortalidade associada a estes tratamentos.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

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.

Evolución clínica en neuromielitis óptica comparando el manejo con azatioprina o rituximab / Clinical evolution in neuromyelitis optica when comparing management with azathioprine and rituximab

RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.

ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.

Rituximab, a Safer Option for Rheumatoid Arthritis: A Comparison of the Reported Adverse Events of Approved Monoclonal Antibodies

Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.

Tratamiento con rituximab en 2 pacientes con lupus eritematoso sistémico pediátrico

Introducción . El LES pediátrico (LESp) representa el 15% de todos los pacientes con LES. La afectación renal y neuropsiquiátrica es más agresivo en el LESp, siendo la afectación de un solo órgano la forma clínica de aparición más común. Formas de presentación como infarto cerebral y serositis son manifestaciones poco frecuentes en el LESp. El tratamiento de un LESp no difiere al de las formas adultas y el arsenal terapéutico es el mismo. El rituximab (RTX) es un agente biológico utilizado a nivel mundial en LES con excelentes resultados, sin embargo, aún no existe consenso sobre su eficacia real en LESp. Objetivos . Presentación de 2 casos de LESp con infarto cerebral y serositis como forma de presentación, que no respondieron a la terapia convencional pero sí a RTX. Métodos . Reporte de caso, con descripción del cuadro clínico, método diagnóstico y forma de tratamiento. Resultados. Primer caso: mujer de 16 años que consulta por cefalea progresiva con crisis tónico-clónica. La tomografía cerebral mostró un infarto cerebral frontoparietal izquierdo. En el examen físico se encontró livedo reticularis en miembros inferiores, dolor articular, caída del cabello y úlceras orales. Las pruebas revelaron anemia normocítica, trombocitopenia, disminución del complemento, 1/320 ANA con patrón homogéneo, 3.200 mg de proteína en muestra de orina de 24 horas y anticuerpos antifosfolipídicos negativos. Se realizó diagnóstico de LESp con compromiso renal, neurológico y hematológico, decidiendo uso de metilprednisolona 1 g EV diario durante 3 días, para luego pasar a ciclofosfamida 1 g EV mensual por 6 meses. Después de 3 meses persisten proteinuria, fatiga y artralgias. Por este motivo, se decidió utilizar rituximab a una dosis de 375 mg / m2 en días 1 y 15 cada 6 meses. Tras 4 infusiones, la proteinuria desapareció, así como las artralgias y malestar general. Actualmente mantiene scores SLEDAI-2K en remisión, con dosis bajas de prednisona. Segundo caso: niño de 10 años, presentó dolor abdominal difuso con distensión asociada de inicio más o menos abrupto. Se agregó cansancio, dificultad para respirar y palpitaciones. Una radiografía simple de abdomen no mostró niveles hidroaéreos, pero la placa torácica demostró derrame pleural bilateral con agrandamiento de la silueta cardíaca. Un ecocardiograma y una ecografía abdominal reveló derrame pericárdico y ascitis respectivamente. Al examen físico se observó palidez general, edema translúcido de miembros inferiores, roce pericárdico y disminución del soplo vesicular en ambas bases pulmonares. Las pruebas de laboratorio mostraron leucopenia, linfopenia, anemia normocítica, reactantes de fase aguda elevados, ANA 1/560, anti-ADN 280 U / mL, complemento disminuido, transaminasas elevadas, urea y creatinina normales. Se diagnosticó LESp y se pulsó con metilprednisolona 30 mg / kg / dosis durante 4 días, para luego pasar a micofenolato 600 mg / m2 diarios. Inicialmente hubo mejoría, pero después de 2 meses reapareció la serositis inicial. Se decidió usar rituximab 375 mg / m2. Después de la segunda infusión la serositis desapareció, normalizándose valores de hemograma, complemento y transaminasas. Actualmente se encuentra en remisión, con dosis bajas de prednisona. Conclusión . Los casos presentados debutaron con infarto cerebral y serositis, mostraron ANA elevados títulos y disminución del complemento. Ambos casos mejoraron con rituximab tras el fracaso a ciclofosfamida y micofenolato. Se obtuvo el consentimiento informado de los padres y los pacientes.

Introduction . Pediatric systemic lupus erythematosus (pSLE) represents 15% of all SLE patients. Renal and neuropsychiatric involvement are more aggressive in pSLE, and single organ involvement is the most commonly found clinical form. Conditions such as cerebral infarction and serositis are unusual manifestation of pSLE. Therapy for pSLE is not different from that for the adult forms, and the therapy armamentarium is the same. Rituximab (RTX) is a worldwide used biological for SLE, with excellent results; however, there is still no consensus with respect to is real efficacy in pSLE. Objectives . Presentation of two pSLE cases with cerebral infarction and serositis as main characteristics, who did not respond to conventional therapy, but who did respond to RTX. Methods . Case report, describing the clinical presentation, diagnostic methods, and therapy approach used. Results . First case: This is a sixteen-year-old girl who was brought because of progressing headache and a tonic-clonic crisis. The brain CT scan showed a left frontoparietal cerebral infarction. Physical examination revealed livedo reticularis in both legs, joint pain, hair loss, and mouth ulcers. Laboratory tests revealed normocytic anemia, thrombocytopenia, reduced complement, 1/320 ANA with a homogeneous pattern, 3.200 mg 24-hour proteinuria, and negative anti-phospholipidic antibodies. A pSLE diagnosis was made, with renal, neurologic, and hematologic involvement, so it was decided to use methylprednisolone, 1 gram IV per day for three days, and then switch to cyclophosphamide 1 g IV per month for 6 months. After three months, proteinuria, fatigue, and arthralgia persisted. For this reason, it was decided to administer rituximab, 375 mg/m2 in days 1 and 15, every six months. After four infusions, proteinuria, joint pain and malaise all disappeared. Nowadays this patient maintains SLEDAI-K scores in remission, and she is also receiving low-dose prednisone. Second case: This is a ten-year-old boy, who presented with abrupt diffuse abdominal pain associated with (abdominal) distention. Other manifestations were tiredness, shortness of breath, and palpitations. A plain abdomen X-ray film did not show hydro-aerial levels, but the chest X-ray film showed bilateral pleural effusion, and enlarged cardiac silhouette. Cardiac ultrasonography and abdominal ultrasonography revealed pericardial effusion and ascites, respectively. Findings in physical examination showed pallor translucid edema of the legs, pericardial throbbing, and reduced respiratory sounds in both pulmonary bases. Laboratory tests revealed leukopenia, lymphopenia, normocytic anemia, elevated acute phase reactants, ANA 1/560, anti-DNA 280 U/mL, reduced complement, elevated transaminases, and normal urea and creatinine. pSLE was diagnosed, and therapy instituted was methylprednisolone 30 mg/Kg/dose for 4 days, then it was switched to mycophenolate 600 mg/m2 per day. There was improvement initially, but after two months, serositis reappeared. Then it was decided to start rituximab 375 mg/m2. After the second infusion, serositis disappeared, and CBC, complement, and transaminase values returned to normal. Nowadays the patient is in remission, and he is receiving low-dose prednisone. Conclusión . Both presented cases featured cerebral infarction and serositis. They also showed high ANA titers and reduced complement. Both patients improved their condition with rituximab after failure with cyclophosphamide and mycophenolate. Informed consent from both parents and patients was obtained.

Comparison of efficacy and safety of rituximab at different doses in the treatment of idiopathic membranous nephropathy / 中华肾脏病杂志

It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m 2 experimental treatment group (375 mg/m 2 once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m 2 experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m 2 experimental treatment group (87.1% vs. 65.8%, χ2=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m 2 experimental treatment group ( χ2=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m 2 experimental treatment group ( χ2=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m 2 experimental treatment group ( χ2=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m 2 experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ2=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m 2 experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m 2 experimental treatment group than that in the 1 g standard treatment group ( Fisher value=8.593, P=0.015). Both 375 mg/m 2 regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m 2 regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.

Three cases of obinutuzumab treatment for rituximab-resistant phospholipase A 2 receptor- associated membranous nephropathy / 中华肾脏病杂志

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Efficacy and safety of half-dose rituximab in the treatment of 23 cases with lupus nephritis / 中华内科杂志

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

Treatment and prognosis analysis of 205 patients with intracranial primary diffuse large B cell lymphoma / 中华放射肿瘤学杂志

Objective:To analyze the clinical efficacy and prognostic factors of intracranial primary diffuse large B-cell lymphoma (DLBCL).Methods:Clinical data of 205 patients pathologically diagnosed with intracranial primary DLBCL at Sun Yat-sen University Cancer center from March 2001 to September 2020 were retrospectively analyzed. Among them, 101 patients were male and 104 female, the median age was 54 years old. Non-germinal center B cell (GCB) subtype accounted for 74.1%(126/170). A total of 177 patients received high-dose methotrexate (HD-MTX) and 91 patients received rituximab. After induction chemotherapy, 59 patients (30.4%) achieved complete response (CR), 112 patients (57.7%) achieved partial response (PR) or stable disease (SD). A total of 83 patients received consolidation or salvage radiotherapy, and only 14 patients received autologous stem cell transplantation (ASCT). The influence of pathological type, chemotherapy, rituximab treatment, radiotherapy and radiotherapy mode, ASCT and other factors on the overall survival (OS) and progression free survival (PFS) was evaluated. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by COX model.Results:The median follow-up time was 34 months. The 5-year OS and PFS rates were 55.6% and 44.2%, respectively. GCB subtype, chemotherapy with HD-MTX, rituximab treatment, remission status after induction chemotherapy, and radiotherapy were favorable prognostic factors for OS or PFS, in which the last three were the independent prognostic factors. Consolidation radiotherapy in patients who obtained CR after induction chemotherapy did not significantly improve survival, while salvage radiotherapy in patients who achieved PR/SD after induction chemotherapy significantly improved both OS and PFS(both P<0.01). Consolidation radiotherapy showed no significant survival difference compared with consolidation ASCT. Conclusions:The non-GCB subtype of intracranial primary DLBCL is related to poor prognosis. The addition of rituximab to HD-MTX based induction chemotherapy can improve survival. Radiotherapy is still an important treatment for intracranial primary DLBCL, and there are limitations of ASCT in practical clinical application.

Comparison of efficacy and safety of BR regimen and R-CHOP regimen in the treatment of newly diagnosed follicular lymphoma / 中国综合临床

Objective:Compare the clinical efficacy and safety of bendamustine combined with rituximab (BR regimen) and rituximab combined with standard CHOP regimen (R-CHOP regimen) in the treatment of newly diagnosed follicular lymphoma (FL).Methods:Adopting a prospective case-control study method. 104 newly diagnosed FL patients admitted to Beijing Aerospace General Hospital from January 2018 to January 2022 were selected and randomly divided into an observation group and a control group using a random number table method, with 52 patients in each group. The observation group was treated with bendamustine combined with rituximab, while the control group was treated with rituximab combined with standard CHOP regimen. Both groups were treated for 6 consecutive courses of treatment, with a 21 day treatment period. Compare the serum lactate dehydrogenase (LDH) levels before and after treatment between two groups β 2-Microglobulin (β 2-microglobulin, β 2-MG level, improvement in quality of life after treatment, long-term survival, clinical efficacy, and incidence of adverse reactions. Measurement data is represented by paired t-tests for intra group comparisons, and independent sample t-tests for inter group comparisons; Counting data is represented as an example (%), and inter group comparisons are made using χ 2-test, Wilcoxon rank sum test was used for comparing rank data. Survival analysis was conducted using the Log Rank test. Results:After treatment, serum LDH and The levels of β 2-MG were lower than before treatment [LDH: (262.34±37.24) U/L ratio (323.45±44.46) U/L, (287.23±43.19) U/L ratio (318.28±52.35) U/L; β 2-MG: (2.72±0.30) mg/L compared to (3.45±0.37) mg/L, (2.93±0.28) mg/L compared to (3.37±0.42) mg/L, t-values of 7.60, 3.30, 11.05, 6.29, P values of <0.001, 0.001, <0.001, <0.001, <0.001], and the observation group was lower than the control group ( t-values of 3.15, 3.69, P values of 0.002, <0.001, respectively). After 6 courses of treatment, the quality of life in the observation group improved in 27 cases, stabilized in 22 cases, and decreased in 3 cases; The quality of life in the control group improved in 18 cases, stabilized in 26 cases, and decreased in 8 cases. The improvement of quality of life in the observation group was better than that in the control group ( Z=-2.03, P=0.042). The progression free survival period in the observation group was longer than that in the control group [52.53 months (95% confidence interval: 49.16-55.89 months) compared to 38.84 months (95% confidence interval: 32.44-45.24 months)], and the difference was statistically significant (Log Rank χ 2=4.06, P=0.044), there was no statistically significant difference in overall survival between the two groups ( P=0.217). The complete remission rate in the observation group was higher than that in the control group [88.46%(46/52) vs 71.15%(37/52)], χ 2=4.83, P=0.028], there was no statistically significant difference in objective response rates between the two groups ( P=0.485). The incidence of nausea, vomiting, leukopenia, neutropenia, alopecia, and fatigue in the observation group was lower than that in the control group, and the differences were statistically significant (all P<0.05). Conclusions:Both the BR regimen and R-CHOP regimen can significantly reduce serum tumor marker levels in the treatment of newly diagnosed FL. However, the BR regimen has a higher complete response rate, better patient quality of life, longer PFS, fewer toxic side effects, and more significant overall efficacy.

Advance in application of rituximab in refractory minimal change disease / 中国医师杂志

Minimally degenerative nephropathy is one of the common types of primary nephrotic syndrome, and it is currently believed that B lymphocytes are closely related to its pathogenesis. Patients with refractory small degenerative kidney disease require treatment with glucocorticoids combined with immunosuppressant. Rituximab is a monoclonal antibody that consumes B cells. Its use in the treatment of patients with refractory microdegenerative kidney disease can reduce recurrence rate, prolong remission period, and reduce hormone exposure. However, there is no consensus on the treatment plan and adverse reaction response measures, and multicenter, prospective, and large-scale research answers are still needed. This article summarizes the latest progress of rituximab in the treatment of refractory minimal degenerative kidney disease, hoping to provide assistance for the development of clinical treatment strategies.

Progress on the mechanism of rituximab in the treatment of primary nephrotic syndrome / 国际儿科学杂志

In recent years, rituximab(RTX) has been increasingly used in the treatment of refractory primary nephrotic syndrome in children, and has achieved positive effects.Experimental evidence suggests that RTX may exert its therapeutic effects by directly acting on B cells and T cells, interfering with the interaction between B cells and T cells, and directly protecting podocytes.However, the number of studies on the mechanism of RTX in the treatment of nephrotic syndrome is limited and there is no definitive evidence, so there is no consensus in the academic community.This article summarizes experimental research results and reasonable speculations put forward by many scholars in recent years, and summarizes the significance of the research on the mechanism of RTX and the existing research gaps in this field, in order to provide theoretical guidance for the clinical application of RTX.

Analysis of incidence and influencing factors of interstitial pneumonia in diffuse large B-cell lymphoma after treatment of R-CHOP-like regimens / 白血病·淋巴瘤

Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.

Pregnancy-associated neuromyelitis optical spectrum disorder combined with primary Sjögren's syndrome: A critical illness case report / 北京大学学报(医学版)

Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.

Research progress in population pharmacokinetics of rituximab / 中国临床药理学与治疗学

Rituximab, a chimeric human-mouse monoclonal antibody, has been used as a first-line treatment for CD20