Cardiovascular events associated with thalidomide and prednisone in leprosy type 2 reaction

Abstract Background: Thalidomide is the drug of choice for the treatment of type 2 leprosy reactions and is often associated with corticosteroids. The use of these drugs in multiple myeloma is associated with the risk of cardiovascular events, but there have been few studies assessing this risk in leprosy patients. Objective: To evaluate the occurrence of cardiovascular events in patients with multibacillary leprosy and their correlation with the use of thalidomide and prednisone. Methods: Analytical cross-sectional study of all patients diagnosed with multibacillary leprosy treated at the Dermatology Service between 2012 and 2022, using electronic medical records. Thromboembolic vascular events, both arterial and venous, including acute myocardial infarction, were considered. The main independent variable was the concomitant use of thalidomide and prednisone during follow-up. Results: A total of 89 patients were included, of which 19 used thalidomide and prednisone concomitantly. There were five cardiovascular events (26.3%), three of which of deep venous thrombosis. The combined use of medications was associated with the events (PR = 6.46 [3.92 to 10.65]; p<0.01). Study limitations: Small number of events, single-center retrospective study. Conclusion: The hypothesis of an association between cardiovascular events and the concomitant use of thalidomide and prednisone is supported, but more robust prospective studies are required for a better assessment.

Cinobufagin Combined with Thalidomide/Dexamethasone Regimen in the Treatment of Patients with Newly Diagnosed Multiple Myeloma of Phlegm and Stasis Obstruction： A Retrospective Study / 中医杂志

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Systemic treatment for severe atopic dermatitis in children: a case series / Tratamiento sistémico para dermatitis atópica grave en niños: una serie de casos

Abstract Background: Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. Methods: We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. Results: We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. Conclusions: Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.

Resumen Introducción: La dermatitis atópica (DA) es la enfermedad inflamatoria crónica de la piel más común en niños. En la mayoría de los pacientes la enfermedad se controla con tratamientos tópicos; sin embargo, algunos pacientes con DA grave no responden a estos tratamientos, por lo que requieren de terapia sistémica. Existe poca información acerca de la dosis ideal, tiempo de uso, respuesta clínica y seguridad del tratamiento sistémico en niños con DA grave. Se realizó este estudio para describir las características clínicas de pacientes con DA grave que requirieron un tratamiento sistémico, los medicamentos utilizados, la evolución clínica, los efectos secundarios y las complicaciones asociadas. Métodos: Se llevó a cabo una revisión retrospectiva de los expedientes de pacientes pediátricos con DA grave atendidos en el Servicio de Dermatología, Instituto Nacional de Pediatría (2000 a 2018), que hayan requerido tratamiento sistémico por más de 3 meses. Resultados: Se incluyeron 21 pacientes. La media de edad de inicio de la enfermedad fue de 3.31 años. Los fármacos utilizados fueron metotrexato (57.1%), talidomida (38%), prednisona (42.8%), azatioprina (19%), mofetil micofenolato (9.5%), ciclosporina (4.7%) y esteroides sistémicos como terapia puente (42.8%). Se observaron efectos secundarios leves en dos pacientes (9.5%) tratados con metotrexato y mofetil micofenolato. Conclusiones: El metotrexato fue el medicamento utilizado en más del 50% de los pacientes con remisión en la mayoría de ellos. La ciclosporina, azatioprina y mofetil micofenolato también fueron efectivos. Los efectos secundarios fueron leves y poco frecuentes. Es necesario realizar estudios comparativos de tratamientos sistémicos para DA grave en la población pediátrica.

Deep Vein Thrombosis Complicating Recurrent Erythema Nodosum Leprosum

Recurrent erythema nodosum leprosum (ENL) is a type 2 leprosy reaction, which often poses a challenge for the treating physician. Patient may be non-ambulatory due to systemic symptoms like fever, body aches, joint pains, and painful skin lesions. Moreover, drugs like corticosteroids and thalidomide in refractory cases pose an increased risk of deep vein thrombosis (DVT). We have described a case who developed DVT in due course of the treatment.

Cuidado clínico farmacêutico e estratégia para o uso racional e adesão ao tratamento em pacientes com hanseníase numa Policlínica do Recife / Pharmaceutical clinical care and strategy to rational use and adhesion to treatment in Hansen's disease patients at a policlinic from Recife

Introdução: a hanseníase é uma doença de fácil diagnóstico, possuindo tratamento e cura. Quando diagnosticada tardiamente, pode trazer graves consequências para os portadores e seus familiares. Uma vez que o tratamento da hanseníase está inserido no componente estratégico da assistência farmacêutica, são exigidos cuidados e orientação. Há necessidade de intervenção clínica farmacêutica, com objetivo de acompanhar prescrições medicamentosas, analisando a adesão dos pacientes ao tratamento com a promoção de ações de educação em saúde, além de minimizar a ocorrência de eventos adversos relacionados aos fármacos do tratamento com possível redução de custos associados aos agravos. Objetivo: realizar o monitoramento para identificar e tratar as possíveis intercorrências que estão comumente presentes no tratamento de hanseníase. Metodologia: a realização do estudo deu-se com o acompanhamento dos pacientes atendidos no serviço de referência a partir da aplicação de questionários em consultas periódic as, vis to que a adesão ao tratamento, reduç ão dos eventos adver sos e controle dos comunic antes são de suma impor tância para o controle epidemiológico. Resultados: os principais sintomas dos indivíduos acometidos foram dormência e eritema nodoso hansênico. A maioria utilizava como tratamento o esquema multibacilar e talidomida. O acometimento relatado dos pacientes foi em nível moderado. Os pacientes possuíam comorbidades como hipertensão, artrose e diabetes. O acompanhamento clínico foi relatado como positivo pela maioria dos entrevistados. Conclusão: o desfecho do estudo mostra que a adesão do paciente é crucial para o êxito do tratamento e o acompanhamento do farmacêutico clínico constitui um pilar positivo, contribuindo para a prevenção de agravos e conscientização da comunidade.

Introduction: Hansen's disease is an easily diagnosed disease, with treatment and cure available. When diagnosed late, it can bring serious consequences for patients and their families. Since the treatment of Hansen's disease is part of the strategic component of pharmaceutical assistance, care and guidance are required. There is a need for clinical pharmaceutical intervention, aiming to monitor drug prescriptions, analyze patients' adherence to treatment while promoting health education actions, in addition to minimizing the occurrence of adverse events related to treatment drugs with possible reduction in costs associated to grievances. Objective:thus, the present study aimed to monitor, identify, and treat possible complications commonly present in the treatment of Hansen's disease. Methodology: The study was carried out with the follow-up of patients seen at the reference service, through the application of questionnaires in periodic appointments, since adherence to treatment, reduction of adverse events and control of communicants are of short importance for epidemiological control. Results:The main symptoms of Hansen's disease patients were numbness and leprosy nodosum erythema. Most used the multibacillary scheme and thalidomide as treatment. The reported involvement of patients was at a moderate level. Patients had other comorbidities such as hypertension, arthrosis and diabetes. The clinical assistance was reported as positive by most interviewees. Conclusion: The outcome of the study shows that patient's compliance is crucial for the success of treatment and the clinical pharmacist's accompaniment is a positive pillar, contributing to the prevention of complications and community awareness.

Tratamiento de la estomatitis aftosa recurrente en pacientes inmunocomprometidos. Revisión sistemática / Treatment of recurrent aphthous stomatitis in immunocompromised patients. Systematic review

RESUMEN Fundamento: Aunque la estomatitis aftosa recurrente no tiene una etiología bien definida porque es una enfermedad multicausal, se ha reconocido que las interacciones o el debilitamiento del sistema inmunitario, contribuyen principalmente a la magnitud del proceso patológico. Las propuestas de tratamiento en pacientes inmunocomprometidos son diversas y por lo general se centran en alteraciones inmunológicas específicas. Objetivo: Evaluar el efecto clínico de los tratamientos propuestos para la estomatitis aftosa recurrente en pacientes inmunocomprometidos. Metodología: La búsqueda se realizó en las bases de datos PubMed/Medline y Cochrane. Se incluyeron ensayos clínicos que tuviesen entre sus variables de respuesta principales: Cicatrización de la úlcera aftosa, tiempo de cicatrización, de recurrencia e intensidad del dolor y entre las variables secundarias: Los efectos adversos y los síntomas. La extracción de datos se realizó de manera independiente por los autores. Se aplicó la metodología por la colaboración Cochrane para evaluar el riesgo de sesgo en cada uno de los estudios. Resultados: Se incluyeron 11 ensayos clínicos (8 controlados) publicados entre 1995 y 2020 y que aportan resultados de la eficacia de varias intervenciones terapéuticas: talidomida (4), irsogladine (2), rebamipida (1), láser de diodo (1), cápsulas de Omega-3 (1), vitamina B 12 (1), Complejo B (1). Seis de estos estudios incluyeron pacientes con la forma menor de estomatitis aftosa recurrente. El periodo de seguimiento estuvo entre los 14 y 360 días. Conclusiones: La talidomida puede ser eficaz en el alivio de los síntomas, la cicatrización y remisión de las lesiones, el diodo de láser y vitamina B12 en la disminución de la intensidad del dolor.

ABSTRACT Background: Although recurrent aphthous stomatitis does not have a well-defined etiology due to it is a multicausal disease, it has been recognized that the interactions or the weakening of the immune system, contribute mainly to the magnitude of the process pathological. Treatment proposals in immune compromised patients are diverse and they usually focus on specific immunological alterations. Objective: To evaluate the clinical effect of the proposed treatments for recurrent aphthous stomatitis in immunocompromised patients. Methodology: The search was performed in the PubMed/Medline and Cochrane databases. Clinical trials were included that could have among their main response variables: Aphthous ulcer healing, healing time, recurrence and pain intensity and among the secondary variables: Adverse effects and symptoms. data extraction was done independently by the authors. The methodology was applied by Cochrane collaboration to assess the risk of bias in each of the studies. Results: 11 clinical trials (8 controlled) published between 1995 and 2020 and that provided the results of the efficacy of various therapeutic interventions: thalidomide (4), irsogladine (2), rebamipide (1), diode laser (1), Omega-3 capsules (1), vitamin B 12 (1), Complex B (1). Six of these studies included patients with the minor form of stomatitis recurrent aphthous. The follow-up period was between 14 and 360 days. Conclusions: Thalidomide may be effective in relieving symptoms, healing and remission of the lesions, the laser diode and vitamin B12 in the decrease of the intensity of the pain.

Hepatotoxicidad por talidomida: caso clínico y revisión de la literatura / Hepatotoxicity by thalidomide: case report and literature review

La talidomida fue desarrollada e introducida al mercado por los laboratorios Grünenthal en 1953, siendo usada principalmente como sedante y también para el tratamiento de las náuseas durante el embarazo. Los informes dan cuenta de aproximadamente 10.000 niños que nacieron con focomelia, dando lugar a la denominada "tragedia de la talidomida", que obligó a su retiro del mercado en 1962. Luego de casi 60 años, es nuevamente utilizada en otros campos de la medicina, entre ellos, para el tratamiento de la lepra y del mieloma múltiple, debido a sus propiedades antinflamatorias, inmunomoduladoras y antiangiogénicas, con expresas advertencias sobre su utilización durante el embarazo; no obstante, con su nuevo uso han sido reportados múltiples efectos adversos, entre los que se encuentra la hepatitis aguda o crónica inducida por este fármaco. Se presenta el caso de una paciente de 34 años con lepra, que estaba en tratamiento con talidomida desde hacía 4 años para combatir las lesiones de piel asociadas a esta enfermedad. Presentó malestar general, vómito, pérdida de peso, artralgias, ictericia, edemas de miembros inferiores, ascitis, coluria y acolia. Se sospechó toxicidad por talidomida, por lo que se suspendió su uso, y se trató con ácido ursodesoxicólico y N-acetilcisteína con mejoría sintomática y de laboratorio, desde la primera semana hasta los 41 días de seguimiento. Las entidades clínicas para las cuales se aprobó talidomida en 1998, pueden traer nuevos problemas y desafíos clínicos. Este caso muestra hepatotoxicidad crónica por talidomida, situación que hasta el momento no se había reportado en la literatura.

Thalidomide was developed and introduced to the market by Grünenthal laboratories in 1953, being used mainly as a sedative and also for the treatment of nausea during pregnancy. Reports give account of approximately 10,000 children who were born with phocomelia, giving rise to the so-called "thalidomide tragedy", which forced its withdrawal from the market in 1962. After almost 60 years, it is usedagain in other fields of medicine, including the treatment of leprosy and multiple myeloma, due to its anti-inflammatory, immunomodulatory and anti-angiogenic properties, with clear warnings about its use during pregnancy; however, multiple adverse effects have been reported in patients with leprosy and multiple myeloma, including acute or chronic hepatitis. We present the case of a 34-year-old patient with leprosy, who had been on thalidomide therapy for 4 years to treat skin lesions associated with this disease. She presented general malaise, vomiting, weight loss, arthralgia, jaundice, lower limb edema, ascites, choluria and acholia. Thalidomide toxicity was suspected, so its use was suspended, and treatment with ursodeoxycholic acid and N-acetylcysteine was initiated, with symptomatic and laboratory improvement from the first week up until 41 days of follow-up. The new range of medical conditions for which thalidomide was approved for in 1998 may bring clinical challenges. This case shows chronic hepatotoxicity due to thalidomide, a situation that had not been reported previously in the literature.

Improvement effects and mechanism of thalidomide on Alzheimer ’s disease model of Caenorhabditis elegans / 中国药房

OBJECTIVE To study the improvement effects and mechan ism of thalidomide on Alzheimer ’s disease （AD）model of Caenorhabditis elegans . METHODS In this study ，the BR 5270 strain of C. elegans was used as AD model and BR 5271 strain as the control. The effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the motility of BR 5270 strains of C. elegans were studied by the basal slowing response assay ；the effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the survival time of BR 5270 strain of C. elegans were studied by life assay ；the effects of thalidomide （0.5，2.0，6.0 mg/mL）on learning and memory ability of BR 5270 strain of C. elegans were studied by short-term and long-term learning and memory assay. RT-PCR technology was used to study the effects of thalidomide （0.5，2.0，6.0 mg/mL）on mRNA expression of phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）signal pathway related genes （Age-1，Akt-1，Gsk-3）and calpain homologous gene （Clp-1）in BR 5270 strain of C. elegans . RESULTS After the intervention of thalidomide ，oscillation times of BR 5270 strain of C. elegans increased significantly within 30 s （except for 0.5 mg/mL group ），and the 10％ of maximum life span was prolonged significantly （only 0.5 mg/mL group ）；the short-term and long-term learning indexes were improved significantly （only 6.0 mg/mL group ）；mRNA expression of Age-1 and Akt-1（except for 0.5，2.0 mg/mL groups ）were increased significantly ，mRNA expression of Gsk-3（except for 0.5 mg/mL group ） and Clp-1 were decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Thalidomide can ameliorate the dyskinesia of AD model of C. elegans，prolong the lifespan of this strain ，and enhance its learning and memory ability. Its mechanism of action may be related to activation of PI 3K/Akt signaling pathway and inhibition of calpain.

Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model / [Avaliação do efeito imunomodulador da talidomida em macrófagos associados a tumores no modelo murino de câncer de mama metastático 4T1]

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Controle e utilização da talidomida: adequados à ampliação do uso e mitigação do risco de teratogenicidade no Brasil? / Thalidomide control and use: are these appropriate to extend the use and mitigate the risk of teratogenicity in Brazil?

Resumo Estudo de utilização de medicamento que descreve o controle da talidomida no Brasil e sua utilização em Minas Gerais. Questionário online foi enviado às unidades federativas do Brasil para coleta de dados de distribuição, dispensação, cadastro de usuários e eventos adversos da talidomida. Dados de distribuição (2011-2018) e dispensação (2015-2018) de Minas Gerais foram obtidos pelo sistema de gerenciamento da assistência farmacêutica. Análise de variância e teste de Tukey foram empregados para comparações dos dados. Das 16 unidades federativas participantes, 100% e 50% utilizavam sistema eletrônico para distribuição e dispensação, respectivamente, e cerca de 43% cadastravam usuários. Sistemas de notificação de eventos adversos eram escassos. Houve redução de 44% na distribuição em Minas Gerais no período. A dispensação manteve-se constante (média 0,0004 DDD/1000 hab./dia) e ocorreu principalmente para eritema nodoso hansênico e mieloma múltiplo. O uso off-label (2,2%) foi crescente. A maioria dos usuários era do sexo masculino (idade média 56 anos). Das mulheres, 30% estavam em idade fértil. A vigilância da talidomida é um desafio em saúde pública. Apesar da ampliação do uso e obrigatoriedade de controle, não há padronização em nível nacional e a notificação de eventos adversos é incipiente.

Abstract Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.

Mieloma múltiple. Experiencia de 9 años en el Hospital Naval Almirante Nef / Multiple myeloma. Nine years' experience at the Hospital Naval Almirante Nef

Introducción: el mieloma múltiple (MM) continúa siendo una enfermedad incurable sin embargo, el trasplante autólogo de médula ósea (TAH), y las drogas antineoplásicas han permitido mejorar la sobrevida global (SG) de los pacientes. Materiales y métodos: estudio de cohorte retrospectivo de 50 pacientes con diagnóstico de MM en el hospital Naval Almirante Nef, desde 2005 a 2013. Los pacientes se dividieron en dos cohortes, según la eligibilidad a trasplante, y analizados acordes a la primera línea de tratamiento y la sobrevida global (SG) hasta abril de 2019. Resultados: mediana de edad 73 años (47-88 años), SG 49 meses, y 50% en etapa-II del Sistema de Etapificación Internacional. La SG de los 39 no candidatos a TAH fue 46 meses; con un mayor número de respuestas completas y sobrevida, con el esquema melfalán-prednisona-talidomida. La SG de los 11 candidatos a TAH fue 66 meses, siendo el esquema bortezomib-ciclofosfamida-dexame-tasona el que concentró un mayor número de respuestas completas libres de progresión. Se trasplantó el 45% de los candidatos, con una mediana de sobrevida de 79 meses versus a los 51 meses de aquellos no trasplantados. Tres casos de neuropatía asociada a talidomida y uno a bortezomib. La SG a los seis meses y a los cinco años de todos los pacientes fue 86% y 44%, respectivamente. Conclusión: la incorpo-ración de nuevos fármacos permitió obtener mejores resultados de sobrevida lo que se condice con estudios nacionales e internacionales.

Introduction: Multiple myeloma (MM) is still an incurable disease however, autologous stem cell transplantation (ASCT), and antineo-plastic drugs have allowed improving the overall survival (OS) of patients. Materials and methods: A retrospective cohort study of 50 patients diagnosed with MM at the Hospital Naval Almirante Nef, from 2005 to 2013. The patients were divided into two cohorts according to transplantation eligibility and analyzed about first-line treatment and overall survival (OS) up to April 2019. Results: Median age 73 years (47-88 years), OS 49 months, and 50% in stage-II International Staging System. OS of the 39 non-candidates for ASCT was 46 months: with a higher number of complete responses and survival, with the melphalan-prednisone-thalidomide scheme. The OS of the 11 candidates for ASCT was 66 months, with the bortezomib-cyclophosphamide-dexamethasone scheme being the one with the highest number of progression-free complete responses. Forty-five percent of the candidates were transplanted, with a median survival of 79 months versus 51 months for those not transplanted. Three cases of neuropathy were associated with thalidomide and one with bortezomib. OS at six months and five years for all patients was 86% and 44%, respectively. Conclusion: The incorporation of new drugs allowed to obtain better survival results, which is by national and international studies.

Prurigo actínico en un centro dermatológico de referencia en Colombia: 108 casos / Actinic prurigo in a dermatological reference center in Colombia: 108 cases

Introducción. El prurigo actínico es una fotodermatosis crónica. Afecta con mayor frecuencia a la población latinoamericana, predomina en mujeres y compromete la piel expuesta al sol, las conjuntivas y los labios. Objetivo. Actualizar la información sobre las características clínico-epidemiológicas y el tratamiento de pacientes con prurigo actínico en Colombia. Materiales y métodos. Se hizo un estudio de corte transversal que incluyó los registros clínicos de pacientes con prurigo actínico atendidos en el Servicio de Fotodermatología del Hospital Universitario Centro Dermatológico Federico Lleras Acosta entre el 2011 y el 2016, y se describieron sus características demográficas, clínicas e histopatológicas, así como su tratamiento. Resultados. Se incluyeron 108 pacientes, el 71,3 % de ellos mujeres y el 28,7% hombres, con predominio de los fototipos III-IV (70 %). La enfermedad se había iniciado durante la primera década de vida en el 66,4% de los casos y el 25 % de los pacientes tenía antecedentes familiares de la enfermedad. Las lesiones predominaban en el rostro (93,5 %), los antebrazos (79,6 %) y el dorso de las manos (70,4 %). También, se documentó compromiso ocular (87,9 %) y de los labios (88,8 %). Se hizo la prueba de fotoprovocación con radiación ultravioleta A en el 25 % de los casos y biopsia cutánea en el 19,4 %. Todos los pacientes se trataron con protección solar química y física. En los casos leves a moderados, se formularon corticoides tópicos (91,7 %) e inhibidores de la calcineurina (65,7 %), y en los graves, talidomida (33,3 %) y pentoxifilina (14,8 %). Conclusión. Las características de los pacientes colombianos con prurigo actínico son similares a las reportadas en otros países latinoamericanos: inicio temprano de la enfermedad, predominio en mujeres, compromiso frecuente de conjuntivas y labios, y adecuada respuesta al tratamiento tópico y sistémico.

Introduction: Actinic prurigo is a chronic photodermatosis. It affects the Latin American population more frequently, predominantly women, and involves the sun-exposed areas of the skin, conjunctiva, and lips. Objective: To update the information on the clinical-epidemiological characteristics and treatment of patients with actinic prurigo in Colombia. Materials and methods: We conducted a cross-sectional study including the medical records of patients with actinic prurigo treated in the Photodermatology Service of Hospital Universitario Centro Dermatológico Federico Lleras Acosta between 2011 and 2016. We described the demographic, clinical, histopathological, and treatment characteristics of the patients. Results: We included 108 patients, 77 (71.3%) were women and 31 (28.7%) men, mainly with phototypes III-IV (70%). The disease had begun during the first decade of life in 66.4% of the cases and 25% of the patients had a family history with the condition. The lesions predominated on the face (93.5%), forearms (79.6%), and back of the hands (70.4%). Ocular (87.9%) and lip (88.8%) involvement was also documented. A photo-provocation test with UVA was performed in 25% of the cases and skin biopsies in 19.4%. Physical and chemical photoprotection was indicated in all patients. Mild to moderate cases were treated with topical corticosteroids (91.7%) and calcineurin inhibitors (65.7%) while severe cases received thalidomide (33.3%) and pentoxifylline (14.8%). Conclusion: The characteristics of actinic prurigo patients in Colombia are similar to those reported in other Latin American countries: early onset of the disease, predominance in women, frequent involvement of conjunctiva and lips, and adequate response to topical and systemic treatment.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

"Descansar e dormir sem riscos": o Jornal do Médico (Portugal) e o desastre da talidomida, 1960-1962 / "Risk-free rest and sleep: " Jornal do Médico (Portugal) and the thalidomide disaster, 1960-1962

Resumo O artigo analisa como o periódico Jornal do Médico, editado na cidade do Porto, em Portugal, divulgou o desastre da talidomida. A pesquisa percorreu as páginas da fonte desde o início de 1960 até o final de 1962. Aqui, objetivam-se apontar e discutir duas questões interligadas: a morosidade em publicar matérias sobre os efeitos deletérios do medicamento, vendido no país sob a denominação Softenon®, e a construção discursiva da isenção da responsabilidade do médico no fenômeno da iatrogenia medicamentosa.

Abstract This article analyzes the way the Porto-based journal Jornal do Médico reported on the thalidomide disaster. The pages of the publication are researched from the beginning of 1960 to the end of 1962 with the aim of identifying and discussing two interconnected questions: the delay in publishing news on the harmful effects of the drug, which was sold in the country under the brand name Softenon®, and the discursive construction of a lack of accountability on the part of physicians for the phenomenon of medication iatrogenesis.

An interesting case of Phocomelia

Authors present a very rare case of tetra-phocomelia evaluated by antenatal ultrasonography. It is a condition seen in 0.62 per 100,000 live births. This is a congenital chromosomal abnormality involving the musculoskeletal system. Primi gravida with spontaneous conception after a long period of infertility underwent early anomaly scan. Patient was not aware of the last menstrual period hence; NT scan was missed. Routine early anomaly scan done between 16-18 weeks of pregnancy diagnosed a fetus with Tetra-Phocomelia. Due to the lack of associated symptoms or significant history, our case did not fit into any specific syndrome and appears to be the result of a sporadic, non-hereditary limb deficiency involving all four limb buds.  Second opinion obtained from a fetal medicine consultant who confirmed the diagnosis. Hence, decided for mid trimester termination and fetus was expelled after 8 hours. Fetus was not sent for pathological analysis. Tetra-phocomelia is a rare congenital anomaly and it may be associated with other deformity also. 1st case of phocomelia was described after the intake of thalidomide. In this condition hands and feet are seen as small flippers of a seal. The differential diagnosis includes sporadic phocomelia, Holt-Oram syndrome, thrombocytopenia-absent radius syndrome (TAR syndrome), Robert’s syndrome, and thalidomide-induced phocomelia. Here authors are presenting a rare case of Phocomelia where there is no history of drug intake or family history. This has to differentiate from thrombocytopenia-absent radius syndrome (TAR syndrome), sporadic phocomelia, Holt-Oram syndrome, Robert’s syndrome, and thalidomide-induced phocomelia.

Rationale use of Thalidomide in erythema nodosum leprosum - A non-systematic critical analysis of published case reports

Abstract INTRODUCTION: Thalidomide is an anti- tumor necrosis factor alpha (TNF-a) drug used mainly in the management of moderate to severe form of Erythema Nodosum Leprosum (ENL). Because of its teratogenic potential it has to be used under proper supervision. Our critical analysis tries to look into the rationale with which it has been used by means of case reports on lepra reaction. METHODS: We looked for the case reports between December 2005 to June 2019 in databases like Pubmed, Embase and other relevant resources. We used search words like "erythema nodosum leprosum(ENL)", "thalidomide", "case report" in different combinations to get relevant reports that focus on thalidomide usage atleast once at any time point during management. The information extracted were indication of thalidomide use, dose, response, outcome, complication if any, along with all the demographic details and geographical distribution. RESULTS: We found 41 case reports eligible for analysis.The information was critically evaluated. From the analysis it was found that 7 of the case report mentioned the exact indication, 4 case report showed irrational use of thalidomide in the case of neuritis without use of steroids, 7 showed proper use of Clofazimine prior to thalidomide initiation, 26 case report showed case report of rationale dose range and in 4 case reports clofazimine was used prior to thalidomide along with the rational dose of thalidomide. CONCLUSIONS: This analysis helps to guide the rationale use of thalidomide focussing on few important points that anyone should keep in mind while managing a case of ENL.

Pharmacovigilance of thalidomide in the Brazilian Health System and patient safety

In Brazil, thalidomide is manufactured by a public laboratory, distributed by the Unified Health System (SUS), and regulated by the National Health Surveillance Agency (Anvisa). Despite the concerns regarding the adverse effects of thalidomide, few drug utilization studies have been conducted to describe processes and outcomes related to this drug. The aim of this study was to elucidate the issues related to the utilization and control of thalidomide, and patient safety within the scope of SUS. In this cross-sectional study, we evaluated the articulation between an outpatient dermatology service of a referral hospital in infectology, the manufacturer, and Anvisa. Four data sources were used: i) interviews with health professionals; ii) data from the Customer Service of the manufacturer, iii) data on adverse events reported to Anvisa, and iv) adverse events identified in outpatient service. Most health professionals interviewed knew the major thalidomide-related adverse effects. None of them ever reported adverse events to Anvisa or contacted the Customer Service. For over three years, there were 330 calls concerning thalidomide at Customer Service, 7% of which were related to adverse events. During a period of six years, Anvisa was notified of only 15 adverse events. Health professionals were aware of the adverse events associated with thalidomide, but not the necessity to report them. The low number of notifications recorded by Anvisa and the information obtained from Customer Service show that pharmacovigilance remains incipient. A pharmacovigilance system that integrates all the services associated with thalidomide is required to strengthen this activity within the SUS to improve patient safety.

Low-dose paclitaxel combined with thalidomide inhibits angiogenesis in mice bearing S180 sarcoma / 中国肿瘤临床

Objective: To investigate the effect of low-dose paclitaxel combined with thalidomide on angiogenesis in mice bearing S180 sarcoma. Methods: An S180 sarcoma-bearing mouse model was established. Forty tumor-bearing mice were randomly divided into four groups: A, the control group, administered normal saline; B, the paclitaxel group, administered 20 mg/kg paclitaxel by intraperitoneal injection three times per week for 2 weeks; C, the thalidomide group, administered 200 mg/kg thalidomide by gavage three times per week for 2 weeks; and D, the paclitaxel + thalidomide group, administered paclitaxel (20 mg/kg) and thalidomide (200 mg/kg) by intraperitoneal/intragastric administration three times per week for 2 weeks. Tumor weight, tumor inhibition rate, microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression were measured. Results: Tumor weight, VEGF expression, and MVD were lower in groups B, C, and D (P<0.05) than in the control. VEGF expression and MVD were lower in group D than in groups B and C; these differences were statistically significant (P<0.05). Conclusions: Low-dose paclitaxel combined with thalidomide exerted an inhibitory effect on vascular growth in S180 sarcoma.

Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma: a single-center study in China / 医学前沿

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.