Methotrexate induced hepatotoxicity in metabolic dysfunction-associated steatotic liver disease

Hepatotoxicity is an under-recognized and potentially fatal side effect of high-dose methotrexate (HDMTX) chemotherapy, and this risk is compounded in children with metabolic dysfunction-associated steatotic liver disease and/or metabolic-associated steatohepatitis. We present the case of a 12-year-old obese, Hispanic male with elevated hepatic transaminases of unknown etiology at initiation of high-risk B-cell acute lymphoblastic leukemia chemotherapy. He developed acute kidney injury within 24 hours of receiving intravenous HDMTX which progressed to acute hepatic failure. Liver biopsy confirmed methotrexate toxicity aggravated by undiagnosed metabolic dysfunction-associated steatotic liver disease. Rapid deterioration precluded liver transplantation, and he died 21 days after HDMTX treatment. This case highlights the need for comprehensive hepatic evaluation in patients with known or suspected liver disease when administering HDMTX. Dialysis should be considered if delayed methotrexate clearance occurs due to potential for rapid, irreversible hepatotoxicity

The descriptive epidemiology of accelerometer-measured physical activity in older adults.

BACKGROUND: Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults. METHODS: Physical activity was measured by uniaxial accelerometry in 4,052 UK (49-91 years) and 3459 US older adults (49-85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent 809 counts/minute is used 18.7% of people reached the 30 min/day threshold. By comparison, 2.5% and 9.5% of American older adults accumulated activity at these levels, respectively. CONCLUSION: As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults.This work was supported by programme grants from the Medical Research Council [G9502233; G0401527] and Cancer Research UK [C864/A8257]. A grant from Research into Ageing [262] funded the 3rd health check clinic. KW is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship [FS/12/58/29709], and AJMC, SJG, NJW, and SB are supported by MRC programme grants [MC_UU_12015/3 and MC_UU_12015/4].This is the final version of the article. It was first available from BioMed Central via http://dx.doi.org/10.1186/s12966-015-0316-

Additional file 1: Figure S1. of The descriptive epidemiology of accelerometer-measured physical activity in older adults

Example accelerometer file showing time segments classified as non-wear using the 90-min and the 60-min zero string criterions. (JPG 80 kb

Additional file 2: Table S1. of The descriptive epidemiology of accelerometer-measured physical activity in older adults

Differences between participants with and without accelerometry at 3rd health check, EPIC-Norfolk. (XLSX 17 kb