ABSTRACT

La prise en charge de la polyarthrite rhumatoïde (PR) chez les sujets drépanocytaires reste un défi dans les pays de l'Afrique subsaharienne. Une patiente âgée de 33 ans drépanocytaire était atteinte de polyarthrite rhumatoïde immunopositive, déformante. Le diagnostic était posé devant une polyarthrite bilatérale symétrique intéressant les grosses et petites articulations des membres avec des facteurs rhumatoïdes et des anticorps anti-CCP2 positifs. Elle développa une anémie sévère sous méthotrexate (MTX), entraînant son arrêt. Malgré un traitement par hydroxychloroquine, l'activité de sa PR demeurait intense et nécessitait des biothérapies pour un contrôle optimal. Cependant, ces traitements restent inaccessibles dans notre contexte.

The management of rheumatoid arthritis (RA) in patients with sickle cell disease remains a challenge in sub-Saharan Africa. A 33-year-old female patient with sickle cell disease had immunopositive, deforming rheumatoid arthritis. The diagnosis was made in the presence of symmetrical bilateral polyarthritis of the large and small joints of the limbs with rheumatoid factors and positive anti-CCP2 antibodies. She developed severe anaemia on methotrexate (MTX), leading to its discontinuation. Despite treatment with hydroxychloroquine, her RA remained intensely active and required biotherapies for optimal control. However, these treatments remain inaccessible in our context

ABSTRACT

RESUMEN La eritrodermia es un síndrome inflamatorio cutáneo grave que se caracteriza por eritema y descamación generalizada en más del 90 % del cuerpo. Este síndrome puede ser la etapa final de diversas enfermedades dermatológicas o el inicio de ciertas patologías como la psoriasis, que es la causa más común. Las enfermedades febriles son causa de exacerbaciones de psoriasis. Se cree que el virus actúa como un superantígeno y activa la inmunidad celular causando cambios inmunológicos con clínica variada en individuos predispuestos. Presentamos el caso de un paciente de sexo masculino que debuta con una forma grave de psoriasis posterior a infección por chikungunya.

ABSTRACT Exfoliative dermatitis is a severe cutaneous inflammatory syndrome characterized by generalized erythema and scaling over more than 90 % of the body. This syndrome can be the final stage of various dermatological diseases or the beginning of certain pathologies such as psoriasis, which is the most common cause. Febrile illnesses are cause of psoriasis exacerbations. It is believed that the virus acts as a superantigen and activates cellular immunity causing immunological changes with varied symptoms in predisposed individuals. We present the case of a male patient who presented with a severe form of psoriasis after chikungunya infection.

ABSTRACT

RESUMEN Divulgamos el caso de una paciente con psoriasis vulgar que presento empeoramiento de la misma luego de infección por Chikungunya, sin mejoría del brote con el tratamiento habitual de la psoriasis, en quien posteriormente se realiza el diagnóstico de Linfoma Hodgkin tipo clásico. Se inició tratamiento quimioterápico y se observó una mejoría completa de las lesiones cutáneas de la psoriasis.

ABSTRACT We report the case of a patient with psoriasis vulgaris who presented worsening of the disease after infection with Chikungunya, with no improvement of the outbreak with the usual treatment for psoriasis, in whom a diagnosis of classic Hodgkin lymphoma was subsequently made. Chemotherapy treatment was started and a complete improvement of the skin lesions of psoriasis was observed.

ABSTRACT

Introducción: el metotrexato se usa ampliamente para el tratamiento de una variedad de enfermedades neoplásicas y autoinmunes. Sin embargo, como todo fármaco, su eficacia viene marcada por cierto grado de toxicidad debido a la farmacocinética del medicamento. El metotrexato se creó como un fármaco anticancerígeno; sin embargo, se ha convertido en el tratamiento de elección contra la artritis reumatoide. Principalmente, el metotrexato causa inflamación de las mucosas epiteliales. La mayoría de los efectos secundarios del metotrexato se pueden detectar de forma temprana y son reversibles. La mucositis del tracto alimentario es el principal efecto secundario de la quimioterapia contra el cáncer. Se le conoce colectivamente como lesión de la mucosa inducida por quimioterapia, afecta todo el canal alimentario desde la boca hasta el ano, ocasionando la mucositis oral y la mucositis intestinal. Material y métodos: se buscaron casos clínicos en los que se reporte mucositis causada por metotrexato en tratamiento de artritis reumatoide. Se empleó un diagrama de flujo, PRISMA modificado para la búsqueda de artículos. Finalmente, se cotejó que los casos clínicos cumplieran con los fundamentos de la CARE guide, para manejar una correcta estructura y bajo riesgo a sesgo. Conclusiones: una correcta anamnesis y exploración clínica oral es lo más importante de la medicina oral. Es relevante indagar sobre las enfermedades que presentan los pacientes, así como la historia de medicamentos que se administren, especialmente en pacientes mayores, con mayores padecimientos de enfermedades sistémicas (AU)

Introduction: methotrexate is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, like all drugs its efficacy is marked by a certain degree of toxicity due to the pharmacokinetics of the drug. Methotrexate was developed as an anticancer drug, however, it has become the treatment of choice for rheumatoid arthritis. Methotrexate primarily causes inflammation of the epithelial mucous membranes. Most of the side effects of methotrexate can be detected early and are reversible. Mucositis of the alimentary tract is the main side effect of cancer chemotherapy. It is collectively known as chemotherapy-induced mucosal injury, affecting the entire alimentary canal from the mouth to the anus, where oral mucositis and intestinal mucositis are both common. Material and methods: we searched for clinical cases reporting mucositis caused by methotrexate in the treatment of rheumatoid arthritis, using a modified PRISMA flowchart to search for articles. Finally, the clinical cases were checked for compliance with the fundamentals of the CARE guide, in order to manage a correct approach to oral medicine. It is important to inquire about the diseases the patients present, as well as the history of medications administered, especially in older patients, with more systemic disease conditions, structure, and low risk of bias. Conclusion: a correct anamnesis and oral clinical examination is the most important aspect of oral medicine. It is important to inquire about the diseases that the patients present, as well as the history of medications that are administered, especially in older patients with major systemic diseases (AU)

ABSTRACT

Introducción: desde 2002, el Grupo Argentino para el Tratamiento de la Leucemia Aguda (GATLA) implementa protocolos del grupo Berlín-Frankfurt-Münster (BFM) como tratamiento estándar de las recaídas de la leucemia linfoblástica aguda (LLA). En 2010, el BFM generó el protocolo IntReALL 10, que en la Argentina se implementó con las limitaciones propias de la región. Población y métodos: 180 pacientes menores de 18 años fueron tratados entre 2010 y 2015 por una LLA recaída de alto riesgo en la Argentina siguiendo un protocolo de recaída del BFM que comparó en forma abierta el tratamiento estándar con una terapéutica innovadora (experimental); esta incluyó el fármaco clofarabina. Se evaluaron 171 pacientes, de los cuales 78 pacientes fueron aleatorizados en forma centralizada (ensayo clínico) y 93 fueron asignados a una de las ramas según el criterio del grupo tratante (cohorte prospectiva). La cohorte donde la asignación del tratamiento no fue aleatorizada fue analizada realizando un ajuste por sexo, edad y por la presencia o no de síndrome de Down, cromosoma Philadelphia e inmunofenotipo T. Resultados: los pacientes que recibieron el tratamiento experimental tuvieron peores resultados (el doble de mortalidad a cinco años) que los que recibieron tratamiento estándar. Esta diferencia alcanzó significancia estadística tanto en el ensayo clínico (p=0,001) como en la cohorte prospectiva (p=0,0009). Conclusiones: nuestros resultados avalan continuar con la rama estándar de los protocolos tipo BFM para el tratamiento de las recaídas de la LLA y fueron concordantes con las conclusiones del grupo ALLIC-REC. (AU)

Introduction: since 2002, the Grupo Argentino para el Tratamiento de la Leucemia Aguda (GATLA) has been implementing protocols from the Berlin-Frankfurt-Münster (BFM) group as the standard treatment for relapses of acute lymphoblastic leukemia (ALL). In 2010, BFM developed the IntReALL 10 protocol, implemented in Argentina with the inherent limitations of the region. Population and Methods: we treated a total of 180 patients under 18 years of age between 2010 and 2015 for high-risk relapsed acute lymphoblastic leukemia (ALL) in Argentina following a BFM relapse protocol. This protocol openly compared standard treatment with an innovative (experimental) therapeutic approach that included Clofarabine. Out of these, 171 patients were assessable, with 78 patients being centrally randomized in a clinical trial, and 93 were assigned to one of the arms based on the treating group's criteria (prospective cohort). The cohort where the treatment assignment had not been randomized, was analyzed with adjustments for gender, age, and the presence or absence of Down Syndrome, Philadelphia Chromosome, and T-cell immunophenotype. Results: patients who received the experimental treatment had worse outcomes (double the five-year mortality) compared to those who received the standard treatment. This difference reached statistical significance in the clinical trial (p=0.001) and the prospective cohort (p=0.0009). Conclusions: our results support the continuation of the standard arm in BFM-type protocols for relapsed ALL treatment and were consistent with the conclusions of the ALLIC-REC group. (AU)

ABSTRACT

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

ABSTRACT

@#Pemphigus foliaceous is a rare autoimmune blistering disease, while psoriasis is a common immune‑mediated inflammatory skin disease. The coexistence of psoriasis and pemphigus foliaceous has rarely been reported. We report a case of a 55‑year‑old Filipino female with an 8‑year history of chronic plaque‑type psoriasis biopsy‑proven. After 5 years, she developed generalized flaccid bullae and crusted erosions over the face, trunk, and extremities, with no mucous membrane involvement. Skin punch biopsy, direct immunofluorescence, and enzyme‑linked immunosorbent assay were consistent with pemphigus foliaceous. The combination of topical corticosteroids and oral methotrexate was selected as the therapeutic approach, leading to a notable improvement in the patient’s condition. This case report underscores the significance of identifying the simultaneous presence of psoriasis alongside autoimmune blistering diseases like pemphigus foliaceous. Examining predisposing and triggering factors, performing re‑biopsy, and further work‑up as the disease evolves may yield more profound insights. Nonetheless, effectively managing this condition poses a significant challenge.

ABSTRACT

Introdução: Uma alta prevalência de doença hepática esteatótica metabólica (MASLD) tem sido descrita na psoríase. A influência da presença de fatores metabólicos, dos polimorfismos dos genes PNPLA3 e TM6SF2 e da dose acumulada de metotrexate (MTX) na progressão da doença esteatótica necessita melhor avaliação. O risco cardiovascular também é aumentado na MASLD e a presença de ateroesclerose subclínica pode representar um marcador do processo inflamatório que une os componentes da hipótese do eixo hepato-dérmico na psoríase. Objetivos: Avaliar o impacto dos polimorfismos dos genes PNPLA3 e TM6SF2, dos parâmetros metabólicos e da dose cumulativa de MTX na esteatose e fibrose hepática avançada em pacientes com psoríase. Avaliar a associação de esteatose e fibrose hepática avançada com ateroesclerose subclínica nestes pacientes. Métodos: Estudo transversal com inclusão prospectiva de pacientes ambulatoriais com psoríase, submetidos a análise clínica e laboratorial, elastografia hepática transitória (TE) com controlled atenuated parameter (CAP) com o equipamento FibroScan® (Echosens,Fr). Todos os pacientes realizaram a genotipagem para os polimorfismos PNPLA3/TM6SF2. A medida da velocidade de onda de pulso carótido-femoral (VOP-cf) foi adotada como medida de rigidez aórtica (rAO). A esteatose foi definida por CAP ≥275 dB/m, fibrose hepática avançada como rigidez hepática ≥10 kPa, aumento da rAo como VOP-cf ≥10m/s. Dose cumulativa significativa de metotrexato foi definida por ≥1500 mg (MTX1500). A análise de regressão logística avaliou as variáveis independentes relacionadas à esteatose e fibrose hepática avançada e ao aumento da rigidez aórtica; valor de p<0,05 foi considerado significativo. Resultados: Foram incluídos 199 pacientes (idade 54,6 ±12,6 anos, 57,3% mulheres). A prevalência de síndrome metabólica (SM), esteatose e fibrose hepática avançada foi de 55,8%, 54,8% e 9%, respectivamente. As frequências dos genótipos PNPLA3 e TM6SF2 foram CC 42,3%/CG 49,5%/GG 8,2% e CC 88,7%/ CT 11,3%/TT 0%. SM (OR3,01 IC95% 1,51- 5,98; p=0,002) e índice de massa corporal (OR1,17 IC95% 1,08-1,26; p<0,01) foram independentemente associados à esteatose. Diabetes Mellitus tipo 2 (DM2) (OR10,76 IC95% 2,42-47,87; p=0,002) e a presença de pelo menos um alelo PNPLA3 G (OR5,66 IC95% 1,08-29,52; p=0,039) foram associados à fibrose hepática avançada, mas não o polimorfismo TM6SF2 ou dose cumulativa de MTX. Para a análise das variáveis relacionadas com o aumento da rAo, um sub-grupo com 80 pacientes (idade 56,2±11,5 anos, 57,5% mulheres, IMC 28,6±5,3kg/m2), com prevalências de SM, DM2, dislipidemia, hipertensão arterial sistêmica, esteatose e fibrose hepática avançada de 57,5%, 40,0%, 67,5%, 70,0%, 50,0% e 16,3%, respectivamente, foi avaliado. Com relação ao tratamento da psoríase, 45% receberam dose de MTX≥1500 mg e 33,8%, tratamento imunobiológico. Neste grupo, a prevalência deVOP-cf≥10m/s foi de 21,2%. Na análise de regressão logística, a idade foi independentemente relacionada com o aumento da rAo (OR: 1,21; IC95%:1,06-1,38; p=0,003), mas não a esteatose ou fibrose hepática avançada. MTX1500 foi um fator protetor cardiovascular (OR: 0,18; IC95%: 0,038-0,87; p=0,033), mas não a terapia imunobiológica. Conclusões: Em indivíduos com psoríase, SM e DM2 conferem maiores chances de esteatose e fibrose avançada, respectivamente. O alelo PNPLA3 G, mas não o polimorfismo TM6SF2, impacta em risco 5 vezes maior de fibrose hepática avançada. O aumento da rAo é associado à idade, mas não à esteatose ou fibrose avançada. Um efeito cardiovascular protetor do MTX foi encontrado em uma população psoríase com alta prevalência de SM e seus componentes.(AU)

Introduction: A high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been described in psoriasis. The influence of the presence of metabolic factors, PNPLA3 and TM6SF2 gene polymorphisms and the cumulative dose of methotrexate (MTX) on the progression of steatotic disease requires further evaluation. Cardiovascular risk is also increased in MASLD and the presence of subclinical atherosclerosis may represent a marker of the inflammatory process that joins the components of the hepato-dermal axis hypothesis in psoriasis. Objectives: To evaluate the impact of PNPLA3 and TM6SF2 gene polymorphisms, metabolic parameters and cumulative MTX dose on steatosis and advanced liver fibrosis in patients with psoriasis. To evaluate the association of steatosis and advanced fibrosis with subclinical atherosclerosis. Methods: Cross-sectional study with prospective inclusion of outpatients with psoriasis, submitted to clinical and laboratory analysis, transient elastography (TE) with controlled attenuated parameter (CAP), with FibroScan® (Echosens,Fr). All patients underwent genotyping for PNPLA3/TM6SF2 polymorphisms. The measurement of carotid-femoral pulse wave velocity (PWV-cf) was adopted as a measure of aortic stiffness (AoS). Steatosis was defined by CAP ≥275 dB/m, advanced liver fibrosis as liver stiffness ≥10 kPa, increased AoS as PWV-cf ≥10m/s. Significant cumulative dose of methotrexate was defined as ≥1500 mg (MTX1500). Logistic regression analysis evaluated the independent variables related to to steatosis and advanced liver fibrosis and increased AoS; p value <0.05 was considered significant. Results: 199 patients were included (age 54.6 ±12.6 years, 57.3% feminine). The prevalence of metabolic syndrome (MetS), steatosis and advanced liver fibrosis was 55.8%, 54.8% and 9%, respectively. The frequencies of the PNPLA3 and TM6SF2 genotypes were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/CT 11.3%/TT 0%. MetS (OR3.01 95% CI 1.51-5.98; p=0.002) and body mass index (OR1.17 95% CI 1.08-1.26; p<0.01) were independently associated with steatosis. Type 2 Diabetes Mellitus (DM2) (OR10.76 95% CI 2.42-47.87; p=0.002) and the presence of at least one PNPLA3 G allele (OR5.66 95% CI 1.08-29.52; p =0.039) were associated with advanced liver fibrosis, but not the TM6SF2 polymorphism or cumulative dose of MTX. To analyze the variables related to increased AoS, a sub-group with 80 patients (age 56.2±11.5 years, 57.5% feminine, BMI 28.6±5.3kg/m2), with prevalences of MetS, DM2, dyslipidemia, systemic arterial hypertension, steatosis and advanced liver fibrosis of 57.5%, 40.0%, 67.5%, 70.0%, 50.0% and 16.3%, respectively, was evaluated. Regarding psoriasis treatment, in this group, 45% received a dose of MTX≥1500 mg and 33.8%, immunobiological treatment. The prevalence of PWVcf≥10m/s was 21.2%. In the logistic regression analysis, age was independently related to increased AoS (OR: 1.21; 95% CI: 1.06-1.38; p=0.003), but not steatosis or advanced liver fibrosis. MTX1500 was a cardiovascular protective factor (OR: 0.18; 95% CI: 0.038-0.87; p=0.033), but not immunobiological therapy. Conclusions: In individuals with psoriasis, MetS and DM2 confer a greater risk for steatosis and advanced fibrosis, respectively. The PNPLA3 G allele, but not the TM6SF2 polymorphism, impacts a 5-fold increased risk of advanced liver fibrosis. Increased AoS is associated with age, but not with steatosis or advanced fibrosis. A protective cardiovascular effect of MTX was found in a psoriasis population with a high prevalence of MetS and its components.(AU)

ABSTRACT

Introducción: la osteomielitis crónica no bacteriana (CNO) es una enfermedad autoinflamatoria ósea y se manifiesta con un amplio espectro clínico, presentándose con afectación monofocal o multifocal. Dado que no es siempre multifocal o recurrente, o ambas, fue propuesto que CNO se utilice como un término que comprenda a todas las presentaciones y la osteomielitis multifocal crónica recurrente (CRMO) se utilice para formas recurrentes y multifocales. Objetivo: presentar un caso clínico inédito, de baja prevalencia a nivel mundial, en una adolescente portadora de una enfermedad autoinflamatoria ósea que planteó desafíos diagnósticos y terapéuticos. Descripción: adolescente, mujer, 11 años, previamente sana que se presentó con dorso-lumbalgia invalidante de un mes de evolución, sin otra sintomatología asociada. Tras varias consultas en emergencia, ingresa a planta de internación pediátrica del Hospital Central de las Fuerzas Armadas (HCFFAA) en octubre de 2021. Resonancia nuclear magnética (RNM) de columna evidencia foco de edema óseo en cuerpo de T11, hemograma normal; VES 48 mm/h, ANA, anti-DNA, FR y HLA B27 negativos. Resultados: luego de descartar procesos infecciosos, oncohematológicos y una vez obtenido el resultado de una biopsia por punción ósea que evidenciaba elementos inflamatorios, se llegó al diagnóstico de CNO en el mes de febrero de 2022, tiempo récord comparando este caso con la literatura internacional. El diagnóstico de esta entidad clínica promedio a nivel mundial es de 12 meses.

Introduction: chronic Non-Bacterial Osteomyelitis (CNO) is an autoinflammatory bone disease that presents a broad clinical spectrum with monofocal or multifocal involvement. Since it is not always multifocal and/or recurrent, it was proposed that CNO be used as a term that encompasses all presentations and Chronic Recurrent Multifocal Osteomyelitis (CRMO) for recurrent and multifocal forms. Objective: to present an unprecedented low prevalence clinical case of an adolescent carrier of an autoinflammatory bone disease that posed diagnostic and therapeutic challenges. Description: a previously healthy female adolescent, 11 years old presented disabling lower back pain for a month without other associated symptoms. After several emergency consultations, she was admitted to the pediatric hospitalization at the Armed Forces Hospital (HCFFAA) in October 2021. A spine MRI showed a T11 body bone edema focus, normal blood count; ESR 48 mm/h, ANA, Anti DNA, RF and negative HLA B27. Results: after ruling out infectious and oncohematological processes, and once the result of a bone puncture biopsy was obtained, which showed inflammatory elements, an ONC diagnosis was made in February 2022, a record time comparing this case with the international literature. The average diagnosis of this clinical condition worldwide is 12 months.

Introdução: a Osteomielite Crônica Não Bacteriana (CNO) é uma doença óssea autoinflamatória, manifestando-se com amplo espectro clínico, apresentando-se com acometimento monofocal ou multifocal. Como nem sempre é multifocal e/ou recorrente, foi proposto que CNO seja usado como um termo que engloba todas as apresentações e Osteomielite Multifocal Recorrente Crônica (OMC) e que seja usado para formas recorrentes e multifocais. Objetivo: apresentar um caso clínico inédito, de baixa prevalência mundial, no caso de uma adolescente portadora de uma doença óssea autoinflamatória que representou desafios diagnósticos e terapêuticos. Descrição: adolescente do sexo feminino, 11 anos, previamente saudável, apresentava há um mês dorso-lombalgia incapacitante sem outros sintomas associados. Após várias consultas de urgência, foi internada na enfermaria pediátrica do Hospital Central das Forças Armadas (HCFFAA) em outubro de 2021. RM da coluna mostra foco de edema ósseo no corpo de T11, hemograma normal; ESR 48 mm/h, ANA, Anti DNA, RF e HLA B27 negativos. Resultados: após a exclusão de processos infecciosos e onco-hematológicos e obtido o resultado de uma biópsia por punção óssea, que evidenciou elementos inflamatórios, o diagnóstico de CNO foi feito em fevereiro de 2022, tempo recorde comparando este caso com a literatura internacional. A média de diagnóstico dessa entidade clínica no mundo é de 12 meses.

ABSTRACT

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.

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic condition that affects the digestive tract and can lead to inflammation and damage to the intestinal lining. IBD patients with cancer encounter difficulties since cancer treatment weakens their immune systems. A multidisciplinary strategy that strikes a balance between the requirement to manage IBD symptoms and the potential effects of treatment on cancer is necessary for effective care of IBD in cancer patients. To reduce inflammation and avoid problems, IBD in cancer patients is often managed by closely monitoring IBD symptoms in conjunction with the necessary medication and surgical intervention. Anti-inflammatory medications, immunomodulators, and biologic therapies may be used for medical care, and surgical options may include resection of the diseased intestine or removal of the entire colon. The current study provides a paradigm for shared decision-making involving the patient, gastroenterologist, and oncologist while considering recent findings on the safety of IBD medicines, cancer, and recurrent cancer risk in individuals with IBD. We hope to summarize the pertinent research in this review and offer useful advice. (AU)

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

ABSTRACT

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.

ABSTRACT

@#Psoriasis is a systematic immune-mediated inflammatory disease where there is an increased cell turnover of the skin leading to scaling, drying, and erythema. The occurrence of pemphigus foliaceus, an autoimmune blistering disease (AIBD) characterized by flaccid bullae and erosions, is rare when concomitantly present with psoriasis. Treatment options for these diseases may overlap. We report a case of a 44-year-old female who presented with both psoriasis and pemphigus foliaceus successfully treated with methotrexate.

ABSTRACT

@#Hypertrophic lichen planus (HLP) is a papulosquamous eruption presenting with extremely pruritic hyperkeratotic flat-topped papules, plaques, and nodules. This is a case of 38-year-old male who presented with a 2-month history of generalized erythematous-to-hyperpigmented papules, patches, and plaques topped with white-to-gray oyster shell-like scales on a background of hyperpigmented macules and patches. There was no involvement of the conjunctival, otic, oral, and genital mucosae, and palmar and plantar aspects of the hands and feet. Dermoscopy showed reticular pearly white structures corresponding to the Wickham striae, comedo-like openings, blue-gray dots, brownish-black dots, and scales. Histopathologic examination revealed marked compact hyperkeratosis, wedge-shaped hypergranulosis, irregular saw-toothed epidermal acanthosis, scattered dyskeratotic keratinocytes, and superficial perivascular lichenoid infiltrate of lymphocytes, histiocytes, and melanophages. The patient was managed as a case of HLP. He was started on methotrexate 10 mg per week, bath psoralen photochemotherapy (PUVA) three times a week, betamethasone valerate 1mg/g cream twice a day for 2 weeks alternating with tacrolimus 0.1% ointment twice a day for another 2 weeks, 10% lactic acid, emollients, and sunscreen. After 6 months of treatment, there was almost 80% improvement of lesions and relief of pruritus.

ABSTRACT

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

ABSTRACT

OBJECTIVE@#To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPIscysc, Cockrofi-Gault, CKD-EPIScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary.@*RESULTS@#All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPIscysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05).@*CONCLUSION@#Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPIscysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.

ABSTRACT

OBJECTIVE@#To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients.@*METHODS@#Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP).@*RESULTS@#The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05).@*CONCLUSION@#For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.