Search

Background: HIV testing among patients with malignant lymphoma (PWML) is variably implemented. We evaluated HIV testing among PWML, and mapped factors influencing hematologists' testing behavior. Materials: We conducted a mixed-methods study assessing HIV testing among PWML, factors influencing HIV testing and opportunities for improvement in five hospitals in the region of Amsterdam, the Netherlands. The proportion of PWML tested for HIV within 3 months before or after lymphoma diagnosis and percentage positive were assessed from January 2015 through June 2020. Questionnaires on intention, behavior and psychosocial determinants for HIV testing were conducted among hematologists. Through twelve semi-structured interviews among hematologists and authors of hematology guidelines, we further explored influencing factors and opportunities for improvement. Findings: Overall, 1,612 PWML were included for analysis, including 976 patients newly diagnosed and 636 patients who were referred or with progressive/relapsed lymphoma. Seventy percent (678/976) of patients newly diagnosed and 54% (343/636) of patients with known lymphoma were tested for HIV. Overall, 7/1,021 (0.7%) PWML tested HIV positive, exceeding the 0.1% cost-effectiveness threshold. Questionnaires were completed by 40/77 invited hematologists, and 85% reported intention to test PWML for HIV. In the interviews, hematologists reported varying HIV testing strategies, including testing all PWML or only when lymphoma treatment is required. Recommendations for improved HIV testing included guideline adaptations, providing electronic reminders and monitoring and increasing awareness. Conclusions: Missed opportunities for HIV testing among PWML occurred and HIV test strategies varied among hematologists. Efforts to improve HIV testing among PWML should include a combination of approaches. [ABSTRACT FROM AUTHOR]

Background: This single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation. Methods: 109 patients were randomly assigned to the 18-week exercise intervention or the usual care control group. The primary outcomes included physical fitness (VO2peak and Wpeak determined using a cardiopulmonary exercise test; grip strength and the 30s chair stand test) and fatigue (Multidimensional Fatigue Inventory) and were assessed prior to randomization and after completion of the intervention or at similar time points for the control group. Multivariable multilevel linear regression analyses were performed to assess intervention effects. Results: Patients in the intervention group attended 86% of the prescribed exercise sessions. Of the patients in the control group, 47% reported ≥10 physiotherapy sessions, which most likely included supervised exercise, suggesting a high rate of contamination. Median improvements in physical fitness ranged between 16 and 25% in the intervention group and between 12 and 19% in the control group. Fatigue decreased in both groups. There were no significant differences between the intervention and control group. Conclusion: We found no significant beneficial effects of the supervised high intensity exercise program on physical fitness and fatigue when compared to usual care. We hypothesized that the lack of significant intervention effects may relate to suboptimal timing of intervention delivery, contamination in the control group and/or suboptimal compliance to the prescribed exercise intervention. Trial registration: Netherlands Trial Register—NTR2341. [ABSTRACT FROM AUTHOR]

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling. [ABSTRACT FROM AUTHOR]