Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer.

PURPOSE: We evaluated T- and B-cell receptor (TCR and BCR) repertoire diversity and 38 serum cytokines in pre- and post-treatment peripheral blood of 66 patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy plus durvalumab and assessed associations with pathologic response and immune-related adverse events (irAEs) during treatment. METHODS: Genomic DNA was isolated from buffy coat for TCR and BCR clonotype profiling using the Immunoseq platform and diversity was quantified with Pielou's evenness index. MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel was used to measure serum cytokine levels, which were compared between groups using moderated t-statistic with Benjamini-Hochberg correction for multiple testing. RESULTS: TCR and BCR diversity was high (Pielou's index > 0.75) in all samples. Baseline receptor diversities and change in diversity pre- and post-treatment were not associated with pathologic response or irAE status, except for BCR diversity that was significantly lower post-treatment in patients who developed irAE (unadjusted p = 0.0321). Five cytokines increased after treatment in patients with pathologic complete response (pCR) but decreased in patients with RD, most prominently IL-8. IFNγ, IL-7, and GM-CSF levels were higher in pre-treatment than in post-treatment samples of patients who developed irAEs but were lower in those without irAEs. CONCLUSION: Baseline peripheral blood cytokine levels may predict irAEs in patients treated with immune checkpoint inhibitors and chemotherapy, and increased post-treatment B-cell clonal expansion might mediate irAEs.

The association between prenatal pyrethroids exposure and children's health - current research.

Exposure to pyrethroids, a widely used agricultural, forestry, and household insecticide, is a major public health concern due to its potential health effects on children. The aim of this review was to summarize the current knowledge of the effects of prenatal exposure to pyrethroids on the course and outcome of pregnancy, health status, and neurobehavioural development of children. A systematic and comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted during January-February 2024. The review included original articles published in peerreviewed English-language journals since 2015. Based on keywords, 198 studies were identified and screened for eligibility. Ultimately, the review analyzed 25 articles including 16 that assessed the effects of prenatal exposure to pyrethroids on children's neurobehavioural development, 3 studies that assessed the effects on the course and outcome of pregnancy, and further 3 focused on respiratory disease. In addition, 1 study analyzed the development of obesity and 2 studies examined the effects on children's growth, weight and body composition in early childhood. In conclusion, there is considerable uncertainty about the adverse effects of prenatal exposure to pyrethroids on children's health. The strongest evidence has been reported for neurobehavioural development although results are also inconsistent. Further research is needed to understand the mechanisms of action and health effects of pyrethroids in susceptible populations. Int J Occup Med Environ Health. 2024;37(4).

Prenatal polyunsaturated fatty acids and atopic dermatitis and food allergy in children from Polish Mother and Child Cohort study.

OBJECTIVES: Polyunsaturated fatty acids (PUFAs) are involved both in immune system regulation and inflammation. The aim of this prospective study was to evaluate the association between maternal dietary intake of PUFAs during pregnancy and atopic dermatitis (AD) and food allergy (FA) in their children up to 7-9 years of age. MATERIAL AND METHODS: The study population consists of 557 mother-child pairs from the Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire completed between the 20-24th weeks of pregnancy, n-3 and n-6 PUFAs as well as n-6:n-3 fatty acid ratio were estimated using food composition tables. Children's health examinations at the age of 1, 2, and 7-9 years were performed by an allergist. Generalized estimating equations were performed in order to assess the prevalence of AD and FA at 3 time points. Independent variables in the equation were n-3, n-6 PUFAs and n-6:n-3 PUFAs ratio. In addition multivariate models were performed to assess the association of PUFAs with AD and FA. RESULTS: The prevalence of AD was 37%, 26% and 21% and FA 26%, 22% and 22% at age of 1, 2 and 7-9 years, respectively. Higher n-6:n-3 fatty acid ratio correlated with higher prevalence of AD at age of 7-9 years (p < 0.07). In multivariate model n-6 PUFAs were significantly associated with increased risk of persistent FA (OR = 1.5, 95% CI: 1.1-2.1). CONCLUSIONS: These results may contribute to the existing knowledge on the impact of maternal diet during pregnancy on children's optimal health, however further studies are needed before drawing conclusions and creating clinical practice guidelines. Int J Occup Med Environ Health. 2023;36(3):428-36.