A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials.

BACKGROUND: Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0-84 years. METHODS: We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 µmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. RESULTS: Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 µmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 µmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. CONCLUSION: After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0-84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients.

Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

INTRODUCTION: High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. METHODS: A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. RESULTS: Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. CONCLUSIONS: These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed.

Aportes a una antropología feminista de la salud: el estudio del ciclo menstrual / Contributions to a feminist anthropology of health: the study of the menstrual cycle

RESUMEN La antropología médica o de la salud centrada en el estudio de las mujeres sigue constituyendo una de las áreas principales del quehacer antropológico en el Estado español. A partir de los aportes de dos referentes de la antropología feminista de la salud como Marcia Inhorn y Mari Luz Esteban, se revisan los hallazgos de una investigación cualitativa sobre del ciclo menstrual, en la que se realizaron 20 entrevistas a mujeres de 16 a 44 años, entre 2013 y 2014, en el municipio de Madrid. El análisis muestra cómo la menstruación es un claro ejemplo de la esencialización reproductiva de las mujeres, del reduccionismo biológico, de la medicalización de los cuerpos de las mujeres y, sobre todo, de su uniformización. La visibilización y cuestionamiento de estos supuestos, a través de las voces de las mujeres entrevistadas, pone de manifiesto la relevancia de este campo dentro de la antropología médica.

ABSTRACT Medical or Health Anthropology focused on the study of women continues to be a main area of anthropological study in Spain. The contributions of two referential figures in feminist health anthropology, Marcia Inhorn and Mari Luz Esteban, are applied to review the findings of a qualitative research study on the menstrual cycle carried out through 20 interviews with women between the ages of 16 and 44 years, between 2013 and 2014, in the municipality of Madrid. The analysis shows that menstruation is a clear example of the reproductive essentialization of women, of biological reductionism, of the medicalization of women's bodies and, above all, of the standardization of bodies. The visibilization and questioning of these assumptions through the voices of the women interviewed highlight the importance of this field within medical anthropology.

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead.

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.