Análise das gestações ectópicas íntegras tratadas com o protocolo de dose única de metotrexato / Analysis of unruptured ectopic pregnancies treated with single-dose methotrexate protocol

Objetivo: Avaliar o índice de sucesso do tratamento da gravidez ectópica com o protocolo de dose única do metotrexato e verificar sua correlação com variáveis clínicas e dados dos exames complementares. Métodos: É um estudo epidemiológico observacional, analítico, retrospectivo, de delineamento transversal. Foi realizado de janeiro de 2014 a agosto de 2020 em um hospital público, de ensino, em nível terciário, do Sul do Brasil. Em 73 casos com diagnóstico de gestação ectópica íntegra, foi utilizado o protocolo de dose única de metotrexato intramuscular, com a dose de 50 mg/m2 de superfície corporal. As variáveis do estudo foram relacionadas ao sucesso do tratamento e abordaram as características clínicas na admissão, dos exames complementares e do tratamento realizado. As variáveis foram comparadas por análise de regressão de Poisson. O nível de significância estabelecido foi de p < 0,05. Resultados: O índice de sucesso foi de 83,6%, e em nove casos foi necessária uma segunda dose da medicação. Nível de ß-hCG inicial superior a 5.000 mUI/mL foi relacionado a menor chance de sucesso (odds ratio ajustado de 0,20 [0,05-0,95]). Tamanho da imagem anexial, presença de líquido livre na cavidade abdominal e demais variáveis estudadas não afetaram a chance de sucesso do tratamento. Conclusão: O protocolo de dose única de metotrexato mostrou-se uma opção válida para o tratamento da gestação ectópica íntegra, notadamente quando o nível de ß-hCG inicial é inferior 5.000 mUI/mL.

Objective: The purpose of the present study is to evaluate the success rate of treatment of ectopic pregnancy with the single-dose methotrexate protocol and to verify its correlation with clinical variables and complementary exam data. Methods: This is a retrospective epidemiological observational analytical cross-sectional study. It was carried out from January 2014 to August 2020 in a tertiary level teaching hospital in southern Brazil. In 73 cases with a diagnosis of intact ectopic pregnancy, the intramuscular methotrexate single-dose protocol was applied with a dose of 50 mg/m2 of body surface. The study variables were related to the success of the treatment and addressed the clinical characteristics on admission, the complementary exams and the treatment performed. The variables were compared by Poisson regression analysis. The level of significance was set at p < 0.05. Results: The success rate was 83.6%, and in nine cases a second dose of the medication was necessary. An initial ß-hCG level greater than 5,000 mIU/mL was related to a lower chance of success (adjusted odds ratio of 0.20 [0.05- 0.95]). The size of the adnexal image, the presence of free fluid in the abdominal cavity and other variables studied did not affect the chance of a successful treatment. Conclusion: The methotrexate single-dose protocol proved to be a valid option for the treatment of intact ectopic pregnancy, notably when the initial ß-hCG level is below 5,000 mIU/mL.

Coriorretinopatia de Birdshot: relato de caso e perspectivas sobre o tratamento / Birdshot chorioretinopathy: a case report and perspectives on its treatment

RESUMO A coriorretinopatia de Birdshot é uma uveíte posterior bilateral crônica rara que acomete, preferencialmente, mulheres de meia-idade. O quadro clínico é composto de pouco ou nenhum processo inflamatório de segmento anterior, associado a vitreíte e lesões coriorretinianas ovoides branco-amareladas de característica hiperfluorescente na angiofluoresceinografia e hipofluorescente na angiografia com indocianina verde. O tratamento se dá por meio de corticoides e outras drogas imunossupressoras. Todavia, em alguns casos, a doença é refratária a tal terapêutica, sendo necessário lançar mão de outras drogas, como os agentes biológicos. O presente artigo busca relatar um caso de coriorretinopatia de Birdshot em ajuste de terapia imunossupressora que evoluiu com má resposta às drogas iniciais e bom controle após uso de imunobiológico e discutir as opções terapêuticas disponíveis atualmente.

ABSTRACT Birdshot chorioretinopathy is a rare chronic bilateral posterior uveitis that preferentially affects middle-aged women. The clinical picture is composed of little or no anterior segment inflammatory process, associated with vitritis and yellowish-white ovoid chorioretinal lesions with hyperfluorescent characteristics on fluorescein angiography and hypofluorescent characteristics on green indocyanine green angiography. Treatment is with corticosteroids and other immunosuppressive drugs. However, in some cases, the disease is refractory to such therapy, making it necessary to resort to other drugs such as biological agents. The present article seeks to report a case of Birdshot chorioretinopathy in an adjustment of immunosuppressive therapy that evolved with poor response to the initial drugs and good control after the use of immunobiologicals and discuss the currently available therapeutic options.

Carcinoma de células escamosas de la lengua / Squamous cell carcinoma of the tongue

Las neoplasias de la lengua son los tumores más comunes de la cavidad bucal y la mayoría pertenecen a carcinomas de células escamosas. Presentamos dos casos de carcinomas de la lengua, correspondientes a un carcinoma escamoso moderadamente diferenciado y un carcinoma verrugoso, en mujeres de mediana edad con factores de riesgo oncogénicos. Estos tumores pueden tener diversos grados de diferenciación, los cuales determinan su pronóstico y tratamiento.

Tongue neoplasms are the most common in the oral cavity, and the majority correspond to squamous cell carcinomas. We present two cases of tongue carcinomas, corresponding to moderately differentiated squamous cell carcinoma and verrucous carcinoma, in middle-aged women with oncogenic risk factors.These tumors can have various degrees of differentiation, which determine their prognosis and treatment.

Morfea superficial / Superficial morphea

La morfea superficial es una variante rara de morfea que se distingue de la clásica tanto en la clínica como en la histopatología. Se caracteriza por máculas hipopigmentadas o hiperpigmentadas, con mínima o ninguna induración, sin síntomas asociados, contractura ni atrofia. En la histopatología, se observa un compromiso limitado a las fibras colágenas en la dermis reticular superficial. Se comunica el caso de una paciente con diagnóstico de morfea superficial tratada con fototerapia ultravioleta B y metotrexato.

Superficial morphea is a rare variant of morphea that is distinguished from the classic variant both clinically and histopathologically. It is characterized by hypo or hyperpigmented patches with minimal to no induration, without associated symptoms, without contracture or atrophy. At the histopathological level, a limited involvement of collagen fibers is observed at the level of the uperficial reticular dermis. The case of a patient with superficial morphea treated with ultraviolet B phototherapy and methotrexate is presented.

Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

Queratoacantoma tratado con metotrexato intralesional: una alternativa terapéutica efectiva en casos seleccionados / Keratoacanthoma treated with intralesional methotrexate: an effective therapeutic alternative in selected cases

El Queratoacantoma es un carcinoma de células escamosas de rápido crecimiento, cuyo tratamiento definitivo contempla la resección quirúrgica. El manejo se dificulta cuando las condiciones de la lesión implican cirugías extensas o las condiciones del paciente son riesgosas al plantear manejo invasivo. Se propone el uso de Metotrexato intralesional como estrategia terapéutica alternativa al tratamiento quirúrgico tradicional. Se exponen 2 casos en los cuales se usó este método. Primero es una paciente de 91 años con queratoacantoma en región frontal, de rápido crecimiento. Segundo, un paciente de 76 años, en tratamiento anticoagulante, con lesión en cuero cabelludo. Ambos pacientes reciben inyecciones de Metotrexato, las cuales muestran resultados significativos, en cuanto a reducción de tamaño. La inyección intralesional de Metotrexato demuestra utilidad como alternativa terapéutica o como manejo neoadyuvante previo a la cirugía

Keratoacanthoma is a rapidly growing squamous cell carcinoma, which definitive treatment includes surgical resection. Therapy becomes more complex when the lesion requires extensive surgeries or the patient's conditions are risky for invasive management. The use of intralesional methotrexate is proposed as an alternative therapeutic strategy to traditional surgical treatment. Two cases are presented where this method was used. First a 91-year-old patient with rapidly growing keratoacanthoma in the frontal region. Second a 76-year-old patient, undergoing anticoagulant treatment, with a scalp lesion. Methotrexate injections were applied to both patients, with significant lesion size reduction. Intralesional injection of Methotrexate proves useful as a therapeutic alternative or as neoadjuvant management prior to surgery.

Moderate to severe plaque psoriasis - treatment with drugs of the classic scheme

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Bone Marrow Mesenchymal Stem Cells Regulate Coagulation and Inflammation Together in Methotrexate Induced Lung Injury Rat Model

Abstract Clinical research has shed the light on the relation between coagulation and inflammation. Coagulation cascade is activated in lung injury resulting in thrombotic and fibrotic lesions. Such a cascade is initiated by inflammation, then the two systems intense each other. New therapies that modulate coagulation and inflammation will be more successful than therapies targeting only one of them. Mesenchymal stem cells showed anti-inflammatory functions in animal models. The role of mesenchymal stem cells in methotrexate induced lung injury model was evaluated, but no studies scoped on the role of stem cells in coagulation associated with inflammation in such models. This study focuses on the therapeutic role of mesenchymal stem cells against the development of clotting in methotrexate induced lung injury rat model. Results showed that mesenchymal stem cells treatment for 4 weeks caused a decrease in lung activated coagulation factors; protease activated receptor-1, fibrinogen, plasminogen activator inhibitor-1 and platelet count with a decrease in inflammatory factors; tumor necrosis factor-α, interferon- γ, interleukin-8, monocyte chemoattractant protein-1 and total leukocyte count. Thus, mesenchymal stem cells have anti-inflammatory potency against clotting risk in methotrexate induced lung injury model. This opens the outlook for stem cells as a new therapy that moderates coagulation associated with inflammation.

Coroidite multifocal / Multifocal choroiditis

Resumo A coroidite multifocal é uma doença inflamatória idiopática pouco comum na prática oftalmológica, que usualmente acomete mulheres jovens. Os autores visam relatar um caso de coroidite multifocal em seguimento ambulatorial em que o paciente foi submetido a injeção subtenoniana de triancinolona associada a corticoterapia via oral com manejo da terapia imunossupressiva. São discutidos os aspectos clínicos, diagnósticos e tratamento. A injeção de triancinolona subtenoniana apresentou bons resultados quando associada à terapia imunossupressiva via oral sobre o edema macular, em consonância com os registros obtidos na literatura médica atual.

Abstract Multifocal choroiditis is an uncommon idiopathic inflammatory ophthalmological disease, which usually affects young women. The authors report a case of multifocal choroiditis in which patient underwent subtenonian triamcinolone injection associated with oral corticosteroid and management of immunosuppressive therapy. The clinical, diagnostic and treatment aspects are discussed. The subtenonian triamcinolone injection presented good results on macular edema when associated with oral imunosuppressive therapy, in agreement with the records obtained in the current medical literature.

Síndrome de Stevens-Johnson asociado al tratamiento con metotrexato de la leucemia linfoblástica aguda: a propósito de un caso / Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report

La necrólisis epidérmica tóxica y el síndrome de StevensJohnson son enfermedades mucocutáneas raras que están asociadas a una evolución prolongada y a un desenlace potencialmente mortal. Principalmente están inducidas por fármacos y las tasas de mortalidad son muy elevadas. Aunque la piel es la más comprometida, también pueden estar afectados múltiples aparatos o sistemas como el cardiovascular, pulmonar, gastrointestinal y urinario. En este artículo, describimos el caso de un paciente con síndrome de Stevens-Johnson asociado al tratamiento con metotrexato, quien desarrolló insuficiencia cardíaca aguda y hemorragia gastrointestinal además de las manifestaciones en la piel. El paciente recibió un tratamiento satisfactorio con metilprednisolona e inmunoglobulina por vía intravenosa y continuó la quimioterapia con metotrexato.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of StevensJohnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.

Síndrome de degeneración combinada de la médula espinal y radiculopatía en dos pacientes por quimioterapia intratecal con metrotrexato y citarabina: casos clínicos / Spinal subacute combined degeneration after intrathecal chemotherapy: report of two cases

Intrathecal chemotherapy may be complicated with the development of myelopathies or toxic radiculopathies. This myeloradicular involvement, of toxic character, is unpredictable, since these patients have repeatedly received Intrathecal chemotherapy with the same drugs without apparent injury. The toxic effect should be mainly attributed to Cytarabine and not to methotrexate, since the central nervous system lacks Cytidine deaminase, the enzyme that degrades Cytarabine. We report two patients, an 18-year-old woman and a 16 years old male, who received systemic and intrathecal chemotherapy (methotrexate, cytarabine) for the treatment of an acute lymphoblastic leukemia and developed, in relation to this procedure, a spinal subacute combined degeneration. They had a proprioceptive and motor alteration of the lower extremities and neuroimaging showed selective rear and side spinal cord hyper intensity produced by central axonopathy. Two weeks later the woman developed a quadriplegia and the young man a flaccid paraplegia due to added root involvement.

Formulation development and evaluation of colon targeted delayed release methotrexate pellets for the treatment of colonic carcinoma

Colonic carcinoma is one of the most common internal malignancies and is the second leading cause of deaths in United States. Methotrexate (MTX) is a drug of choice in the treatment of colon cancer. The aim of the present research work was to develop and characterize colon targeted pellets of MTX for treatment of colonic carcinoma. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as release retardant in different ratio. Based on the physical appearance, sphericity and % in vitro drug release, batch P17 containing EC: MCC (3:7) was optimized for core pellets. The site specificity was obtained by screening the coating polymers and by coating the core pellets with EudragitS100. The 32 full factorial design was applied in which airflow rate (X1) and coating time (X2) were the independent parameters and physical appearance (Y1) and time taken for 100% drug release (Y2) were selected as the dependent variables. From the results obtained, 6min of coating time and 60cm3/min airflow rate was optimized. The batch B5 showed appropriate physical appearance and % in vitro drug release upto 17hr indicating sustained release property. The ex-vivo studies performed on rat colon indicated a significant relation with the in vitro drug release. The drug release followed Higuchi's model indicating the diffusion pattern of drug release from the matrix of pellets. Thus, the coated pellets can be a good candidate for site specific delivery of MTX to colon by decreasing the gastric irritation and thus to improve bioavailability.

Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for Intravenous Immunoglobulin-Resistant Kawasaki Disease

PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.

Tratamiento conservador del embarazo ectópico en cicatriz de cesárea previa: reporte de un caso clínico / Conservative treatment of the ectopic cesarean scar pregnancy: report of a clinical case

El embarazo localizado dentro de una cicatriz de cesárea previa es el menos frecuente de los embarazos ectópicos y no existe un tratamiento estándar. Se presenta el caso de una paciente de sexo femenino de 33 años de edad, que ingresó por el servicio de emergencias de Ginecología y Obstetricia del Hospital Obrero Nº2, con reporte ecográfico de embarazo de 6,3 semanas, a nivel de cicatriz de cesárea previa, con embrión único con actividad cardiaca; por la solicitud de la paciente de preservar la fertilidad se le ofreció tratamiento médico con metotrexato.

The pregnancy located within the previous cesarean section scar is the less frequent of the ectopics pregnancies and a standard treatment doesn't exist. We present the case of a 33 year-old female patient admitted by the Servicio de Emergencias de Ginecología y Obstetricia del Hospital Obrero Nº2, with ultrasonography report of pregnancy of 6,3 weeks, and ectopic cesarean scar pregnancy, with single embryo with heart activity; By the request of the patient to preserve fertility were offered treatment medical with metotrexato.