Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature.

Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the "real life" risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery.

Nucleotide excision repair is a potential therapeutic target in multiple myeloma.

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM.

Melatonin response to bright light in recovered, drug-free, bipolar patients.

Melatonin suppression by bright light was investigated in 15 drug-free euthymic bipolar patients and control subjects matched for age and sex with the patients. There were no differences between groups on the extent of melatonin suppression by 500 lux bright light administered between 0200h and 0400h. These results do not support the hypothesis that melatonin suppression by bright light is a reliable trait marker in recovered bipolar patients.

Comportamento de diferentes parâmetros extraídos do sinal de EMG em função da força muscular / Behavior of different parameters extracted from the EMG signal as a function of strength

Muitos pesquisadores têm estudado a relação entre a atividade mioelétrica e performance muscular medido como trabalho, torque ou força. No entanto, não existe consenso sobre o melhor parâmetro para este tipo de análise...