During the past few decades and especially during and after the COVID-19 pandemic, the use of nutraceuticals has become increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have an inherent toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies and biomarkers of exposure, effect, and susceptibility appears to play a pivotal role in the safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly or when polypharmacy is involved. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors that influence their safety.

The presence of osteoclast-like giant cells (OGC) in hepatocellular carcinoma (HCC) is rare and literature on this topic is scarce. In this article, we report on a case of a 77-year-old male patient with HCC with OGC and provide an overview of the current literature.

We conducted a systematic search to find all available literature on OGC in HCC. The electronic databases PubMed, Web of Science, Embase and CENTRAL were searched from inception until October 2020.

Thirteen articles on this topic were identified and were included in this review. Data on 14 patients were available, described in twelve case reports, one patient in a patient series and the present case. Median age of included patients was 68 years. Two patients underwent neoadjuvant therapy prior to surgery. Of the 14 cases, eight tumours with OGC arose in a cirrhotic liver. Oncological outcome in this series was unfavourable, even after surgical resection, with a median disease-free survival of 75 d.

The presence of OGC in HCC is rare. Current literature is scarce, and suggests an unfavourable outcome in regard to overall survival of HCC.

Similar to the radiological findings in rapidly destructive arthrosis of the hip joint (RDA), subchondral insufficiency fracture of the femoral head (SIF) can result in progressive femoral head collapse of unknown etiology. We thus examined the osteoclast activity of hip joint fluid in SIF with progressive collapse in comparison with that in RDA. Twenty-nine hip joint fluid samples were obtained intraoperatively with whole femoral heads from 12 SIF patients and 17 RDA patients. SIF cases were classified into subgroups based on the presence of ≥2 mm collapse on preoperative radiographs: SIF with progressive collapse (n = 5) and SIF without progressive collapse (n = 7). The levels of tartrate-resistant acid phosphatase (TRACP)-5b, interleukin-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were measured. The number of multinuclear giant cells at the subchondral region was histopathologically assessed using mid-coronal slice of each femoral head specimen. The median levels of all markers and the median number of multinuclear giant cells in SIF with progressive collapse were significantly higher than those in SIF without progressive collapse, while there were no significant differences in SIF with progressive collapse versus RDA. Regression analysis showed that the number of multinuclear giant cells was positively correlated with the level of TRACP-5b in joint fluid. The present study demonstrated the possible association of increased osteoclast activity with the existing condition of progressive collapse in SIF, which was quite similar to the findings in RDA, indicating that increased osteoclast activity may reflect the condition of progressive collapse in SIF as well as RDA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2987-2995, 2018.