Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer

Adverse effects are the major limiting factors in combinatorial chemotherapies. To identify genetic associations in ovarian cancer chemotherapy-induced toxicities and therapy outcomes, we examined a cohort of 101 patients receiving carboplatin-paclitaxel treatment with advanced high-grade serous ovarian cancers. Based on literature and database searches, we selected 19 candidate polymorphisms, designed a multiplex single nucleotide polymorphism-genotyping assay and applied Cox regression analysis, case–control association statistics and the log-rank Mantel−Cox test. In the Cox regression analysis, the SLCO1B3 rs1052536 AA-genotype was associated with a reduced risk of any severe toxicity (hazard ratio = 0.35, p = 0.023). In chi-square allelic test, the LIG3 rs1052536 T-allele was associated with an increased risk of neuropathy (odds ratio [OR] = 2.79, p = 0.031) and GSTP1 rs1695 G allele with a poorer response in the first-line chemotherapy (OR = 2.65, p = 0.026). In Kaplan–Meier survival analysis, ABCB1 rs2032582 TT-genotype was associated with shorter overall survival (uncorrected p = 0.025) and OPRM1 rs544093 GG and GT genotypes with shorter platinum-free interval (uncorrected p = 0.027) and progression-free survival (uncorrected p = 0.012). Results suggest that SLCO1B3 and LIG3 variants are associated with the risk of adverse effects in patients receiving carboplatin-paclitaxel treatment, the GSTP1 variant may affect the treatment response and ABCB1 and OPRM1 variants may influence the prognosis.     

Family members’ participation in palliative inpatient care: An integrative review

Aim

To analyse how family members participate in hospital inpatient palliative care, and how their participation could be supported.

Methods

This review followed a methodology outlined in the literature for integrative reviews. A literature search supplemented by a manual search was conducted on four electronic databases during 2020 to 2021: PubMed, CINAHL, PsycINFO, and Cochrane Library. A critical appraisal of the included studies was performed, and data were analysed using inductive content analysis.

Results

The literature search resulted in 4990 articles, of which 14 articles were included in this review. Four main categories were identified concerning the participation of family members in hospital inpatient palliative care: participation in the physical care, provision of emotional support, promoting good patient care, and support provided by healthcare professionals for family members’ participation. Family members’ participation can be supported in different ways, including active communication and adequate information.

Conclusion

Family members’ participation in hospital inpatient palliative care has been an important part of palliative care in hospital settings. Family members should be offered the opportunity to participate in patient care, and their presence in the hospital should be accommodated. Research on the topic is still scarce, and future research is needed from different perspectives, including intervention research.     

HLA–B27 modulates nuclear factor κB activation in human monocytic cells exposed to lipopolysaccharide

Objective

To study whether HLA–B27 modifies some key factors controlling inflammatory responses on lipopolysaccharide (LPS) stimulation in human monocytic cells.

Methods

U937 human monocytic cells were stably transfected with either HLA–B27 genomic DNA, HLA–B27 complementary DNA, HLA–A2 genomic DNA, or with the resistant vector pSV2neo (mock) alone. The cells were stimulated with LPS. Electrophoretic mobility shift assay was performed to determine nuclear factor κB (NF‐κB) and heat‐shock factor 1 activities, Western blotting was performed to detect the expressions of inhibitory κBα (IκBα) and heat‐shock proteins (HSPs), and enzyme‐linked immunosorbent assay was performed to measure tumor necrosis factor α (TNFα) secretion.

Results

The expression of HLA–B27 modulated the response to LPS in U937 human monocytic cells. Stimulation with LPS led to faster degradation of IκBα regulatory proteins, accompanied by faster and prolonged activation of NF‐κB in HLA–B27–expressing cells compared with HLA–A2 and mock transfectants. The secretion of TNFα upon LPS stimulation correlated well with the activation of NF‐κB. No activation of the heat‐shock response was observed.

Conclusion

Our data indicate that HLA–B27 has effects on host responses to LPS that are unrelated to antigen presentation. Two crucial events in the development of arthritis, the activation of NF‐κB and the secretion of TNFα, were found to be enhanced in HLA–B27–expressing cells upon LPS stimulation. Because LPS is known to be present in the inflamed joints of patients with reactive arthritis (ReA), the enhanced inflammatory response of HLA–B27–positive cells upon LPS stimulation offers an attractive explanation for the role of HLA–B27 in the development of ReA.

     

Physical performance characteristics of women with fibromyalgia

Objective. The aim of this study was to examine physical performance in women with fibromyalgia (FM) using methods that are easy to use in clinical settings and to compare our findings with published norms or a healthy comparison group. Methods. Measures of shoulder pain and range-of-motion, isometric shoulder endurance, neck rotation, leg strength, hand grip strength, back flexibility, 6-minute walk distance, and symptom duration were completed on 97 subjects with FM. The comparison group was 30 age-matched healthy women. Results. The FM group had significantly lower physical functioning scores on all variables when compared to the healthy group or published norms. When pain at rest was controlled, pain on motion was the most significant predictor of variance in shoulder range of motion, whereas range of motion was the most significant predictor of right shoulder endurance and grip strength of both hands. Conclusions. Women with FM are markedly below average in physical performance abilities when measured by clinical tests.