Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Manejo de la neoplasia trofoblástica gestacional. A propósito de un caso

La enfermedad trofoblástica gestacional es definida como un grupo heterogéneo de lesiones, las cuales surgen a partir del epitelio trofoblástico de la placenta luego de una fertilización anormal. Se presenta el caso de una paciente de 35 años de edad, con diagnóstico de neoplasia trofoblástica gestacional posmolar en etapa I, que se detectó tras estudios imagenológicos de seguimiento y determinación de la hormona gonadotropina coriónica humana, para lo cual llevó tratamiento con quimioterapia y terapéutica de mantenimiento con metotrexato por 5 días o metotrexato/ácido folínico por 8 días, hasta la normalización de la gonadotropina coriónica humana. Lo más relevante es que, aunque estos tumores abarcan menos del 1 % de los tumores ginecológicos, representan una amenaza para la vida de las mujeres en edad reproductiva.

Gestational trophoblastic disease is defined as a heterogeneous group of lesions, which arise from the trophoblastic epithelium of the placenta after abnormal fertilization. The case of a 35-year-old female patient is presented with a diagnosis of posmolar gestational trophoblastic neoplasia in stage I, which was detected after follow-up imaging studies and determination of human chorionic gonadotropin, for which she underwent chemotherapy treatment and maintenance therapy with methotrexate for 5 days or methotrexate/folinic acid for 8 days, until normalization of human chorionic gonadotropin The most relevant thing is that, although these tumors comprise less than 1% of gynecological tumors, they represent a threat to the life of women of reproductive age.

Synthesis, characterization and protection effect of black rice anthocyanins nano-composite against hepatotoxicity induced by methotrexate in rats

Abstract The present study aimed to investigate the beneficial of prepared black rice anthocyanins nano-composite (An-AgNps) against hepatotoxicity induced by methotrexate (MTX) in rats. Anthocyanins nano-composite was prepared by silver as the metallic ion reduction and were characterized by IR and SEM. The rats in our experiment were divided into five groups. Serum lipid profile, serum transaminases (ALT and AST), ALP, LDH, TBA, GSH and SOD were examined. The results show that SEM of An-AgNps has average particle size from 70 to 130nm. In the group treated with MTX; TC, TG, LDL-c, ALT, AST, ALP, LDH and TBA levels were significantly (P0.05) increased than NC, while, HDL-c, SOD and GSH levels were significantly (P0.05) decreased. On the other hand, An-AgNps + MTX treated groups were reversed the levels of all biomarkers similar to NC. In conclusion, the results show that An-AgNps has a protective effect on MTX-induced hepatotoxicity and oxidative stress.

Resumo O presente estudo teve como objetivo investigar o benefício de nanocompósito de antocianinas de arroz preto preparado (An-AgNps) contra a hepatotoxicidade induzida por metotrexato (MTX) em ratos. O nanocompósito de antocianinas foi preparado a partir da prata por meio da redução do íon metálico e caracterizado por IR e SEM. Os ratos em nosso experimento foram divididos em cinco grupos, e foram examinados o perfil lipídico sérico, as transaminases séricas (ALT e AST), ALP, LDH, TBA, GSH e SOD. Os resultados mostram que SEM de An-AgNps tem tamanho médio de partícula de 70 a 130 nm. No grupo tratado com MTX, os níveis de TC, TG, LDL-c, ALT, AST, ALP, LDH e TBA aumentaram significativamente (P 0,05) do que NC, enquanto os níveis de HDL-c, SOD e GSH diminuíram significativamente (P 0,05). Por outro lado, nos grupos tratados com An-AgNps + MTX, foram revertidos os níveis de todos os biomarcadores semelhantes ao NC. Em conclusão, os resultados mostram que o An-AgNps tem um efeito protetor contra a hepatotoxicidade induzida pelo MTX e o estresse oxidativo.

Uso de mifepristona en embarazo ectópico intersticial: un reporte de caso / Use of mifepristone in an interstitial ectopic pregnancy: a case report

Introducción: El embarazo ectópico intersticial es una forma de presentación poco frecuente, con una incidencia del 2-4% de los embarazos ectópicos; sin embargo, a pesar de su baja incidencia la mortalidad es cinco veces mayor, impactando en las cifras de mortalidad materna y representando en torno al 10-15% de los casos. Objetivo: Presentar un caso de embarazo ectópico intersticial, cuya ocurrencia es poco frecuente, así como el abordaje satisfactorio del manejo médico con mifepristona y metotrexato. Caso clínico: Mujer de 28 años con antecedente de resección tubárica por quiste paraovárico derecho, quien acudió a urgencias por hallazgo en ecografía obstétrica de sospecha de embarazo intersticial izquierdo y se le administró manejo farmacológico con dosis de metotrexato y mifepristona, con éxito. Conclusiones: El manejo médico con metotrexato y mifepristona para el embarazo ectópico intersticial parece ser una elección eficaz en los casos con estabilidad hemodinámica y deseo de conservación de la fertilidad.

Background: Interstitial ectopic pregnancy represents a rare form of presentation, with an incidence of 2-4% of all ectopic pregnancies. However, despite its low incidence, it is associated with a five-fold increase in mortality, significantly impacting maternal mortality rates, accounting for approximately 10-15% of cases. Objective: To present a case of interstitial ectopic pregnancy, which is a rare occurrence, as well as the successful medical management approach with mifepristone and methotrexate. Case report: A 28-year-old women with a history of right paraovarian cyst tubal resection presented to the emergency department due to suspected left interstitial pregnancy identified on obstetric ultrasound. The patient was successfully managed with pharmacological treatment using doses of methotrexate and mifepristone. Conclusions: Medical management with methotrexate and mifepristone for interstitial ectopic pregnancy appears to be an effective choice in cases with hemodynamic stability and a desire for fertility preservation.

Tratamiento del embarazo ectópico implantado en cicatriz de cesárea: estudio de cohorte 2018-2022, Lima, Perú / Treatment of ectopic pregnancy implanted on cesarean scar: cohort study 2018-2022, Lima, Peru

Objetivos: Describir las características clínicas y el tratamiento del embarazo ectópico implantado en la cicatriz de cesárea, así como las complicaciones y el pronóstico obstétrico. Materiales y métodos: Estudio de cohorte retrospectivo de gestantes con diagnóstico de embarazo ectópico implantado en la cicatriz de cesárea según los criterios de la Sociedad de Medicina Materno-Fetal, atendidas entre enero de 2018 y marzo de 2022 en dos instituciones de alta complejidad, pertenecientes a la seguridad social, ubicadas en Lima, Perú. Se hizo un muestreo consecutivo. Se midieron variables sociodemográficas y clínicas de ingreso, diagnóstico, tipo de tratamiento, complicaciones y pronóstico obstétrico. Se hace un análisis descriptivo. Resultados: Se incluyeron 17 pacientes, de 29.919 partos. De estas, el 41,2 % recibió tratamiento médico y el resto recibió tratamiento quirúrgico. Se realizó un manejo local exitoso con metotrexato en el saco gestacional en dos pacientes con ectópico tipo 2. Cuatro de las pacientes requirieron histerectomía total. Seis pacientes experimentaron una gestación después del tratamiento, y 4 de ellas culminaron el embarazo con una madre y un neonato saludables. Conclusiones: El embarazo ectópico implantado en la cicatriz de una cesárea es una entidad poco frecuente, para la cual se cuenta con alternativas de manejo médico y quirúrgico con aparentes buenos resultados. Se requieren más estudios con mayor calidad metodológica de asignación aleatoria que ayuden a caracterizar la seguridad y la efectividad de las diferentes alternativas terapéuticas para las mujeres con sospecha de esta patología.

Objectives: To describe the clinical characteristics and treatment of ectopic pregnancy arising in the cesarean section scar, as well as its complications and obstetric prognosis. Material and methods: Retrospective cohort study of pregnant women with the diagnosis of a scar pregnancy in accordance with Maternal-Fetal Medicine Society criteria, seen between January 2018 and March 2022 in two high complexity institutions of the social security system, located in Lima, Peru. Consecutive sampling was used. Baseline sociodemographic and clinical variables were measured, including diagnosis, type of treatment, complications and obstetric prognosis. A descriptive analysis was performed. Results: Out of 29,919 deliveries, 17 patients were included. Of these, 41.2 % received medical management and the rest were treated surgically. Successful management with intra-gestational sac methotrexate was performed in two patients with ectopic pregnancy type 2. Four patients required total hysterectomy. Six patients became pregnant after the treatment and 4 completed their pregnancy with healthy mother and neonate pairs. Conclusions: Ectopic pregnancy implanted in a cesarean section scar is an infrequent occurrence for which medical and surgical management options are available with apparently good outcomes. Further studies of better methodological quality and random assignment are needed in order to help characterize the safety and effectiveness of the various therapeutic options for women with suspected scar pregnancy.

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.

Neurotoxicidad subaguda por metotrexato en pacientes con enfermedad oncohematológica. Reporte de tres casos / Subacute methotrexate neurotoxicity in patients with oncohematological disease. A report of 3 cases

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.

Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.

Protective effect of linoleic acid on liver toxicity induced by methotrexate / Efecto protector del ácido linoleico sobre la toxicidad hepática inducida por metotrexato

SUMMARY: We aimed to investigate the protective effect of linoleic acid on liver toxicity induced by methotrexate. The study was carried out in partnership with the Department of Anatomy and Department of Medical Pharmacology of Çukurova University Faculty of Medicine, using the laboratory facilities of the Department of Medical Pharmacology. Human hepatocyte cell line (CRL- 11233) cells obtained from the American Type Culture Collection Organization (ATCC) were used. Expressions of apoptotic pathway markers, apoptosis inducing factor (AIF), BAX, BCL 2, GADD 153, 78-kDa glucose-regulated protein (GRP78), and CASPASE-3 were evaluated. All analyzes were examined in four groups (Group 1; control, Group 2; linoleic acid given, Group 3; methotrexate given and Group 4; linoleic acid and methotrexate given). The mean ± standard error values of the obtained results as nanogram / milliliter (ng / ml) are in Group I, Group II, Group III and Group IV, respectively; AIF values, 0.4150 ± 0.1208, 0.3633 ± 0.2389, 1.792 ± 0.3611 and 1.077 ± 0.1646, BAX values, 0.900 ± 0.1864, 1.002 ± 0.2098, 8.352 ± 1.467 and 4.295 ± 1.522, BCL 2 values, 13.93 ± 1.198, 13.92 ± 1.739, 2.938 ± 1.059 and 9.250 ± 1.492, GADD 153, 0.7333 ± 0.1751, 0.7067 ± 0.2115, 1.650 ± 0.2950 and 1.237 ± 0.1805, GRP78, 0.4767 ± 0.1804, 0.5233 ± 0.1590, 2.183 ± 0.2639 and 1.112 ± 0.2693, CASPASE-3 values , 1.127 ± 0.2033, 0.8317 ± 0.3392, 13.50 ± 1.871 and 8.183 ± 1.030. It was determined that linoleic acid has a protective effect on methotrexate-induced liver toxicity.

Nuestro objetivo fue investigar el efecto protector del ácido linoleico sobre la toxicidad hepática inducida por metotrexato. El estudio se llevó a cabo en colaboración con el Departamento de Anatomía y el Departamento de Farmacología Médica de la Facultad de Medicina de la Universidad de Çukurova, utilizando las instalaciones del laboratorio del Departamento de Farmacología Médica. Se usaron células de la línea celular de hepatocitos humanos (CRL-11233) obtenidas de la American Type Culture Collection Organisation (ATCC). Se evaluaron las expresiones de marcadores de vías apoptóticas, factor inductor de apoptosis (AIF), BAX, BCL 2, GADD 153, proteína regulada por glucosa de 78 kDa (GRP78) y CASPASE-3. Todos los análisis se examinaron en cuatro grupos (Grupo 1; control, Grupo 2; se administró ácido linoleico, Grupo 3; se administró metotrexato y Grupo 4; se administró ácido linoleico y metotrexato). Los valores medios ± error estándar de los resultados obtenidos como nanogramo/mililitro (ng/ml) se encuentran en el Grupo I, Grupo II, Grupo III y Grupo IV, respectivamente; Valores de AIF, 0,4150 ± 0,1208, 0,3633 ± 0,2389, 1,792 ± 0,3611 y 1,077 ± 0,1646, valores de Bax, 0,900 ± 0,1864, 1,002 ± 0,2098, 8,352 ± 1,467 y 4,295 ± 1,522, BCL 2 valores, 13,93 ± 1,199. 2,938 ± 1,059 y 9,250 ± 1,492, GADD 153, 0,7333 ± 0,1751, 0,7067 ± 0,2115, 1,650 ± 0,2950 y 1,237 ± 0,1805, Grp78, 0,4767 ± 0,1804, 0,5233 ± 0,1590, 2,183, ± 1,263. 1,127 ± 0,2033, 0,8317 ± 0,3392, 13,50 ± 1,871 y 8,183 ± 1,030. Se determinó que el ácido linoleico tiene un efecto protector sobre la toxicidad hepática inducida por metotrexato.

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol / Predição de ruptura por hemograma completo em gestações ectópicas tubárias tratadas com protocolo de dose única de metotrexato

Abstract Objective The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. Materials and Methods A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (β-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. Results The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). Conclusion Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

Resumo Objetivo A disponibilidade de marcadores confiáveis e baratos que podem ser usados para determinar o risco de ruptura durante o tratamento com metotrexato (MTX) em gestações ectópicas (GEs) é considerável. O objetivo do presente estudo é investigar o papel de marcadores inflamatórios sistêmicos, como leucócitos (ou glóbulos brancos, glóbulos brancos), a relação neutrófilo-linfócito (NLR) e largura de distribuição de plaquetas (PDW), que estão entre os parâmetros do hemograma completo (hemograma), na predição de ruptura de PEs sob tratamento com MTX. Materiais e Métodos Foram analisados retrospectivamente 161 pacientes com EP tubária submetidas a protocolo de dose única de metotrexato (MTX), sendo que o grupo controle (n = 83) incluiu pacientes curadas com MTX, enquanto o grupo roto (n = 78) incluíram pacientes operadas por ruptura tubária durante o tratamento com MTX. As características de EP, beta-gonadotrofina coriônica humana (β-hCG), achados ultrassonográficos e marcadores derivados de CBC, como WBC, NLR e PDW, foram investigados comparando os dois grupos. Resultados A RNL foi maior no grupo roto, de 2,92 ± 0,86%, e significativamente menor no grupo controle, de 2,09 ± 0,6%. Da mesma forma, o PDW foi maior (51 ± 9%) no grupo roto, e foi significativamente menor a (47 ± 13%) no grupo controle (p < 0,05). Outros parâmetros do hemograma foram semelhantes em ambos os grupos (p > 0,05). Conclusão Marcadores inflamatórios sistêmicos derivados do hemograma podem ser facilmente aplicados para predizer o risco de ruptura tubária na Eps, uma vez que o hemograma é um exame de baixo custo e fácil aplicação, solicitado primeiramente a cada paciente durante a internação.

Experience of a Tertiary Service in the Treatment of Women with Cervical Pregnancy / Experiência de um serviço terciário no tratamento de mulheres com gravidez ectópica cervical

Abstract Objective Cervical pregnancy is challenging for the medical community, as it is potentially fatal. The treatment can be medical or surgical; however, there are no protocols that establish the best option for each case. The objective of the present study was to describe the cases of cervical pregnancy admitted to a tertiary university hospital over a period of 18 years. Methods A retrospective study based on a review of the medical records of all cervical pregnancies admitted to the Women's Hospital at Universidade Estadual de Campinas, Southeastern Brazil, from 2000 to 2018. Results We identified 13 cases of cervical pregnancy out of a total of 673 ectopic pregnancies; only 1 case was initially treated with surgery because of hemodynamic instability. Of the 12 cases treated conservatively, 7 were treated with single-dose intramuscular methotrexate, 1, with intravenous and intramuscular methotrexate, 1, with intravenous methotrexate, 1, with 2 doses of intramuscular methotrexate, and 2, with intra-amniotic methotrexate. Of these cases, one had a therapeutic failure that required a hysterectomy. Two women received blood transfusions. Four women required cervical tamponade with a Foley catheter balloon for hemostasis. There was no fatal outcome. Conclusion Cervical pregnancy is a rare and challenging condition from diagnosis to treatment. Conservative treatment was the primary method of therapy used, with satisfactory results. In cases of increased bleeding, cervical curettage was the initial treatment, and it was associated with the use of a cervical balloon for hemostasis.

Resumo Objetivo A gravidez ectópica cervical é um desafio para a comunidade médica, pois pode ser fatal. O tratamento pode ser clínico ou cirúrgico, mas não existem protocolos que estabeleçam a melhor opção para cada caso. O objetivo deste estudo foi descrever os casos de gravidez ectópica cervical internados em um hospital universitário terciário durante 18 anos. Métodos Estudo retrospectivo com revisão de prontuários de todas as gestações ectópicas cervicais internadas no Hospital da Mulher da Universidade Estadual de Campinas de 2000 a 2018. Resultados Foram identificados treze casos de gestação ectópica cervical em um total de 673 gestações ectópicas; apenas 1 caso foi inicialmente tratado com cirurgia por causa de instabilidade hemodinâmica. Dos 12 casos tratados conservadoramente, 7 foram tratados com metotrexato por via intramuscular em dose única, 1, com metotrexato pelas vias intravenosa e intramuscular, 1, com metotrexato por via intravenosa, 1, com 2 doses de metotrexato por via intramuscular, e 2, com metotrexato por via intra-amniótica. Desses casos, um apresentou falha terapêutica, e realizou-se uma histerectomia. Duas mulheres receberam transfusões de sangue. Quatro mulheres necessitaram de tamponamento cervical com cateter balão de Foley para hemostasia. Não houve casos fatais. Conclusão A gravidez cervical é uma condição rara e desafiadora desde o diagnóstico até o tratamento. O tratamento conservador foi o principal método terapêutico utilizado, com resultados satisfatórios. Nos casos de sangramento aumentado, a curetagem cervical foi o tratamento inicial, e foi associada ao uso de balão cervical para hemostasia.

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.

Gestación ectópica sobre cicatriz de cesárea

Los embarazos ectópicos en la cicatriz de cesárea previa constituyen una patología infrecuente. Representan la forma más rara de gestación ectópica y ocurren en 1 de cada 2,000 embarazos. En las últimas décadas se está produciendo un aumento de su incidencia relacionado con el aumento del número de cesáreas. Su clínica inconsistente puede retrasar su diagnóstico, por lo que requiere un alto grado de sospecha para su identificación. El diagnóstico se realiza principalmente con la ecografía transvaginal, mediante hallazgo del saco gestacional en la cicatriz de la histerotomía. La escasez de casos reportados en la literatura imposibilita la estandarización de un correcto tratamiento. La insuficiente información disponible junto con las potenciales graves complicaciones hace de esta patología un desafío para todo especialista. Presentamos un caso de gestación ectópica en la cicatriz de cesárea previa que fue diagnosticado ecográficamente y resuelta con tratamiento médico con metotrexato. Se evidencia la importancia del seguimiento, tanto clínico como ecográfico y de los niveles de βhCG hasta la resolución completa.

Ectopic pregnancies in the scar of previous cesarean section are an infrequent pathology. They represent the rarest form of ectopic gestation and occur in 1 in 2.000 pregnancies. In recent decades there has been an increase in its incidence related to the increase in the number of cesarean sections. Its inconsistent clinical presentation may delay its diagnosis, so it requires a high degree of suspicion for its identification. The diagnosis is mainly made with transvaginal ultrasound, by finding of the gestational sac in the hysterotomy scar. The scarcity of cases reported in the literature makes it impossible to standardize correct treatment. The insufficient information available together with the potential serious complications make this pathology a challenge for every specialist. We present a case of ectopic pregnancy in the scar of a previous cesarean section which was diagnosed ultrasonographically and resolved with medical treatment with methotrexate. The importance of followup, both clinical and with ultrasound and βhCG levels until complete resolution, is evident.

Oral Manifestations of Erythema Multiforme due to Methotrexate Intoxication

ABSTRACT: To report a rare case of erythema multiforme (EM) associated with methotrexate (MTX) with cutaneous and oral manifestations and to compare it to existing cases in which MTX was not used for cancer treatment. A 56-years- old female, in physical examination skin lesions and multiple oral ulcers associated with pain during manipulation were observed, and underwent treatment for rheumatoid arthritis with Methotrexate 2.5mg. During examination patient-reported that 15 days ago she had undergone a rheumatoid factor examination, doubling the MTX dosage (10mg / day) without doctor's consent. The diagnostic hypothesis of EM. The medical conduct consisted of the suspension of MTX and prescription of a vitamin complex with folinic acid. Local dental therapy for to control oral lesions, pain control and lip hydration was performed using low-level laser therapy (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), benzydamine hydrochloride spray, purified lanolin for lip dryness, and toothpaste without sodium lauryl sulfate to prevent burning. After 12 days, there was significant remission of oral and skin signs and symptoms, which confirmed the diagnosis was EM due to MTX intoxication. Thorough clinical evaluation and anamnesis favored diagnosis and early multi-professional management provided remission of oral and skin lesions, prevented systemic complications.

RESUMEN: El objetivo de este trabajo fue informar un caso raro de eritema multiforme (EM) asociado a metotrexato (MTX) con manifestaciones cutáneas y orales y compararlo con casos existentes en los que no se utilizó MTX para el tratamiento del cáncer. Caso clínico: Mujer de 56 años, en el examen físico se observaron lesiones cutáneas y múltiples úlceras de la cavidad oral asociadas a dolor durante la manipulación.Se sometió a tratamiento para la artritis reumatoide con metotrexato 2,5 mg. Durante el examen, la paciente informó que hacía 15 días se había sometido a un examen de factor reumatoide, duplicando la dosis de MTX (10 mg / día) sin el consentimiento del médico. La hipótesis diagnóstica de EM. La conducta médica consistió en la suspensión de MTX y prescripción de un complejo vitamínico con ácido folínico. La terapia dental local para el control de las lesiones orales, el control del dolor y la hidratación de los labios se realizó mediante terapia con láser de bajo nivel (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), aerosol de clorhidrato de bencidamina, lanolina purificada para la sequedad de labios y pasta de dientes sin lauril sulfato de sodio para evitar quemaduras. Después de 12 días, hubo una remisión significativa de los signos y síntomas orales y cutáneos, lo que confirmó el diagnóstico de ME por intoxicación por MTX. La evaluación clínica exhaustiva y la anamnesis favorecieron el diagnóstico y el manejo multiprofesional precoz proporcionó la remisión de las lesiones orales y cutáneas, evitando además complicaciones sistémicas.

Methotrexate nephrotoxicity in a patient with preserved renal function. case report

ABSTRACT Introduction: Methotrexate is a drug with chemotherapeutic properties frequently used for the treatment of certain types of cancer. The following is a clinical case which, to the best of the authors' knowledge, is the first report in Colombia on nephrotoxicity caused by this drug and describes the consequences as well as the treatment provided at a quaternary care hospital. Case report: A 71-year-old patient with a diagnosis of non-Hodgkin's lymphoma with normal renal function underwent chemotherapy (high-dose methotrexate intravenously) and developed stage 3 acute renal failure according to the KDIGO guidelines, which was most likely related to methotrexate intake. The patient received treatment with intravenous fluids and sodium bicarbonate as promoters of urine excretion of the toxin, and oral calcium folinate following the institutional protocol. The patient was discharged with recovery of kidney function and improved creatinine and urea nitrogen levels. Conclusion: The treatment given to the patient in this case report shows that although methotrexate nephrotoxicity is a potentially serious entity, it can have a good prognosis if treated promptly.

RESUMEN Introducción. El metotrexato es un fármaco con propiedades quimioterapéuticas usado de forma frecuente para el tratamiento de ciertos tipos de cáncer. A continuación, se presenta un caso clínico que, a conocimiento de los autores, es el primer reporte en Colombia sobre nefrotoxicidad por este medicamento, así como sus consecuencias y el manejo que se le dio en un hospital de cuarto nivel. Presentación del caso. Hombre de 71 años con diagnóstico de linfoma no Hodgkin y función renal normal, quien se sometió a tratamiento quimioterapéutico (metotrexato a altas dosis por vía endovenosa) y desarrolló insuficiencia renal aguda estadio 3 según las guías KDIGO, la cual muy probablemente se relacionaba al consumo de metotrexato. El paciente recibió manejo con líquidos endovenosos y bicarbonato de sodio como promotores de la eliminación renal del tóxico, así como folinato cálcico oral, según el protocolo institucional, con lo cual se logró la recuperación de su función renal y que los niveles de niveles de creatinina y nitrógeno ureico mejoraran. Conclusiones. El manejo del paciente reportado demuestra que aunque la nefrotoxicidad por metotrexato es una entidad potencialmente grave, puede tener un buen pronóstico si se maneja oportunamente.

Embarazo ectópico intramiometrial posterior a fertilización in vitro. Tratamiento conservador con metotrexato intrasacular, seguido de embarazo exitoso luego de transferencia de embriones descongelados

Se describe un caso de embarazo ectópico intramiometrial luego de tratamiento de fertilización in vitro y transferencia embrionaria (FIV-TE). El caso fue tratado conservadoramente mediante inyección de metotrexato intrasacular guiada por ecografía, obteniéndose un embarazo gemelar exitoso a término después de una transferencia de embriones descongelados.

We describe a case of ectopic intramyometrial pregnancy after in vitro fertilization and embryo transfer (IVF-ET), treated conservatively by ultrasound-guided intrasacular injection of methotrexate, followed by a successful twin pregnancy after frozen-thawed embryos transfer.

Malformación arteriovenosa posterior a la retención de productos de la concepción / Arteriovenous malformation after retention of products of conception

Resumen OBJETIVO: Plantear un procedimiento para pacientes con retención de restos corioplacentarios y riesgo de formación de fístulas arteriovenosas que sea efectivo, seguro y ambulatorio. MATERIALES Y MÉTODOS: Estudio de serie de casos, retrospectivo, de pacientes atendidas en el Hospital Gea González de enero a mayo de 2022. Se empleó un equipo de Bettocchi, de flujo continuo de 5 mm, lente cilíndrico de 2.9 mm y 30°. En casos específicos se programó un procedimiento quirúrgico con resectoscopio Richard Wolf Princess, con diámetro exterior de 7 mm, sistema óptico de 2.7 mm, dirección visual de 30°. RESULTADOS: Se revisaron 642 expedientes de los que se obtuvo una serie de 31 casos que se incluyeron conforme a la clasificación de Gutenberg, con biopsia por protocolo posaborto y resección con Grasper para los tipos 0 y 1; dos pacientes se enviaron a Urgencias por sangrado abundante para aspiración mecánica endouterina inmediata; dos pacientes se catalogaron con tipo 3; en la primera se optó por el tratamiento médico con metotrexato con lo que se consiguió la resolución completa y la segunda finalizó el embarazo con histerectomía laparoscópica. CONCLUSIONES: En pacientes con imágenes ecográficas sugerentes de retención de restos corioplacentarios o malformación arteriovenosa, los procedimientos con visión directa evitan las complicaciones inmediatas y futuras. El diagnóstico mediante la clasificación de Gutenberg permite definir el tipo de acceso con extracción en frío con pinza Grasper para los tipos 0 y 1, o la aplicación de una prueba farmacológica con metotrexato y resección histeroscópica para los tipos 2 y 3 en pacientes hemodinámicamente estables.

Abstract OBJECTIVE: To propose an effective, safe and outpatient procedure for patients with retained chorioplacental remnants and risk of arteriovenous fistula formation. MATERIALS AND METHODS: Retrospective case series study of patients attended at the Gea González Hospital from January to May 2022. A Bettocchi equipment was used, 5 mm continuous flow, 2.9 mm cylindrical lens and 30°. In specific cases a surgical procedure was scheduled with a Richard Wolf Princess resectoscope, 7 mm outer diameter, 2.7 mm optical system, 30° visual direction. RESULTS: We reviewed 642 files from which we obtained a series of 31 cases that were included according to the Gutenberg classification, with biopsy by postabortion protocol and resection with Grasper for types 0 and 1; two patients were sent to the ER for heavy bleeding for immediate MVA; two patients were categorized as type 3; in the first one we opted for medical treatment with methotrexate with which we achieved complete resolution and the second one ended the pregnancy with laparoscopic hysterectomy. CONCLUSIONS: In patients with ultrasound images suggestive of retained chorioplacental debris or arteriovenous malformation, direct vision procedures avoid immediate and future complications. Diagnosis by Gutenberg classification allows to define the type of access with cold extraction with Grasper forceps for types 0 and 1, or the application of a pharmacological test with methotrexate and hysteroscopic resection for types 2 and 3 in hemodynamically stable patients.

Tratamiento del embarazo ectópico no complicado con inyección local de metotrexato / Management of uncomplicated ectopic pregnancy with local injection of methotrexate

Resumen OBJETIVO: Describir la experiencia en la atención de pacientes con embarazo ectópico no complicado con una inyección local de metotrexato guiada por ecografía. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo y de serie de casos llevado a cabo del 1 de enero del 2021 al 28 de febrero del 2022 en el Instituto Nacional Materno Perinatal, Lima, Perú. Las participantes tuvieron embarazo ectópico no complicado, tratado con inyección local de metotrexato guiada por ecografía. Los datos se obtuvieron de los registros en las historias clínicas. El análisis estadístico se procesó en el programa SPSS 19. RESULTADOS: Se registraron 222 casos de embarazo ectópico y se aplicaron 11 inyecciones locales con metotrexato guiadas por ecografía. De acuerdo con su localización 4 embarazos fueron tubáricos, 1 cervical y 6 en cicatriz de cesárea. La edad promedio de las embarazadas fue de 34.5 años. El promedio de semanas de embarazo fue de 7. La concentración inicial de b-hCG fue de 42812.55 mU/mL. El tamaño promedio del saco gestacional fue de 22.8 mm. El tamaño medio de los embriones fue de 7.81 mm. Se detectó actividad cardiaca embrionaria en 10 casos que recibieron una inyección intratorácica de cloruro de potasio hasta que no se evidenció el latido cardiaco. Un solo caso recibió una dosis sistémica adicional de metotrexato. Otro caso resultó con hemoperitoneo, por rotura de embarazo ectópico luego de la inyección local. CONCLUSIONES: La inyección local de metotrexato, guiada por ecografía, es una alternativa a otras técnicas quirúrgicas aplicadas para tratar pacientes con embarazo ectópico no complicado, con indicación quirúrgica.

Abstract OBJECTIVE: To describe the experience in the care of patients with uncomplicated ectopic pregnancy with ultrasound-guided local injection of methotrexate. MATERIALS AND METHODS: Retrospective, descriptive, case series study conducted from January 1, 2021 to February 28, 2022 at the Instituto Nacional Materno Perinatal, Lima, Peru. Participants had uncomplicated ectopic pregnancy treated with ultrasound-guided local injection of methotrexate. Data were obtained from medical records. Statistical analysis was processed in SPSS 19. RESULTS: 11 ultrasound-guided local methotrexate injections were performed. According to their location 4 pregnancies were tubal, 1 cervical and 6 in cesarean scar. The average age of the pregnant women was 34.5 years. The average number of weeks of pregnancy was 7. The initial b-hCG concentration was 42812.55 mU/mL. The mean gestational sac size was 22.8 mm. The mean embryo size was 7.81 mm. Embryonic cardiac activity was detected in 10 cases that received an intrathoracic injection of potassium chloride until no heartbeat was evident. A single case received an additional systemic dose of methotrexate. Another case resulted in hemoperitoneum, due to rupture of ectopic pregnancy after local injection. CONCLUSIONS: Ultrasound-guided local injection of methotrexate is an alternative to other surgical techniques applied to treat patients with uncomplicated ectopic pregnancy with surgical indication.

Rosai-dorfman disease: a rare presentation of extranodal involvement of isolated bone. case report

ABSTRACT Introduction: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis, is a rare disorder characterized by histiocyte proliferation. Case presentation: A 33-year-old man consulted the emergency department of a tertiary care institution in Cartagena de Indias, Colombia, due to a 6-month history of progressive deformity in the frontal right side of the face, associated with pain of slow progression, without any other symptoms or dermatological involvement. There were no other major findings on physical examination and laboratory tests performed were negative. Imaging scans obtained showed extensive inflammatory involvement of the frontal bone, which led to suspect osteomyelitis as the first diagnostic possibility. A biopsy of the lesion was performed with negative cultures for bacteria, which allowed establishing a diagnosis of extranodal Rosai-Dorfman disease with isolated bone involvement. Treatment with systemic corticosteroids was indicated with poor response, so methotrexate was added, achieving an evident improvement after 2 months. Conclusions: Little is known about the manifestations of Rosai-Dorfman disease and its treatment in the adult population. The present case report contributes to expanding the literature on this topic, which can present with rare symptoms that may pose challenges for its diagnosis.

RESUMEN Introducción. La enfermedad de Rosai-Dorfman, también conocida como histiocitosis sinusal, es un trastorno poco frecuente caracterizado por la proliferación de histiocitos. Presentación del caso. Hombre de 33 años quien consultó al servicio de urgencias de una institución de tercer nivel de Cartagena de Indias, Colombia, por una deformidad de progresión lenta que apareció 6 meses atrás en el costado frontal derecho de la cara y generaba dolor. Al examen físico no hubo hallazgos mayores y los estudios paraclínicos fueron normales o negativos. Se obtuvieron imágenes que evidenciaron extenso compromiso inflamatorio/infeccioso del hueso frontal, por lo que se sospechó de osteomielitis y se realizó biopsia de la lesión que permitió establecer diagnóstico de enfermedad de Rosai-Dorfman variante extranodal con compromiso óseo aislado. El paciente recibió tratamiento con corticoide sistémico sin obtener respuesta, por lo que se adicionó metotrexato, con lo cual se logró mejoría a los 2 meses. Conclusiones. Las manifestaciones de la enfermedad de Rosai-Dorfman en población adulta son poco conocidas, además no hay mucha información sobre su tratamiento, por lo que el presente caso contribuye a ampliar la literatura sobre esta enfermedad que puede presentarse con sintomatología completamente inusual.

Mastitis granulomatosa idiopática: Caso clínico y revisión literaria / Idiopathic granulomatose mastitis: Case report and literary review

Se describe el caso clínico de una paciente con diagnóstico histológico de mastitis granulomatosa idiopática, enfermedad poco frecuente en la que se utilizan inmunosupresores como tratamiento descripto y puede confundirse con otras entidades atendidas en la especialidad. Se describe el caso y se realiza una revisión de la literatura.

The clinical case of a patient with a histological diagnosis of idiopathic granulomatous mastitis is described, a rare disease in which immunosuppressants are used as the described treatment and can be confused with other entities treated in the specialty. The case is described and a literature review is carried out.