Hearing Loss Detection and Early Intervention Strategies in Kenya

Background: Thirty-four million children globally have disabling hearing loss, with the highest prevalence in low- and middle-income countries (LMICs). Early identification and management is crucial, yet barriers to screening and treatment of hearing loss are extensive in LMICs. Unaddressed hearing loss negatively impacts individuals and communities. The WHO’s 2021 World Report on Hearing urges the development of Ear and Hearing Care (EHC) programs to improve access to all aspects of care, including screening, diagnostics, management, and developmental support. A joint Nairobi- and Seattle-based group convened in 2021 to discuss strategies for program development in Kenya, as presented in this paper. Findings: Developing a national EHC program must include the necessary support services for a child with a diagnosed hearing loss, while simultaneously promoting engagement of family, community, and healthcare workers. Existing government and healthcare system policies and priorities can be leveraged for EHC programming. Strategies for success include strengthening connections between policymakers at national, county, and municipal levels and local champions for the EHC agenda, with a concurrent focus on policy, early detection and intervention, habilitation, and family-centered care. Updates to health policy and funding to support the accessibility of services and equipment should focus on leveraging national healthcare coverage for hearing technologies and services, strengthening referral pathways, training to bolster the workforce, and metrics for monitoring and evaluation. Additional strategies to support forward progress include strategic engagement of partners and leveraging local partners for phased scale-up. Conclusions and Recommendations: Recommendations to strengthen EHC within the Kenyan health system include concurrent leverage of existing health policies and priorities, partner engagement, and strengthening referral pathways, monitoring and evaluation, and training. These strategies may be generalized to other countries too

Lenalidomide-induced upregulation of CD80 on tumor cells correlates with T-cell activation, the rapid onset of a cytokine release syndrome and leukemic cell clearance in chronic lymphocytic leukemia

In chronic lymphocytic leukemia (CLL) lenalidomide causes striking immune activation, possibly leading to clearance of tumor cells. This study shows that upregulation of CD80 on tumor cells and T-cell activation, which appears to be dispensable for the drug’s anti-tumor effects, correlate with unique toxicities of lenalidomide in CLL. This provides a rationale for combinations of lenalidomide with immunosuppressive agents. See related perspective article on page 1198

The lymph node microenvironment promotes B-cell receptor signaling, NF-κB activation, and tumor proliferation in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes, involves blood, bone marrow, and secondary lymphoid organs such as the lymph nodes (LN). A role of the tissue microenvironment in the pathogenesis of CLL is hypothesized based on in vitro observations, but its contribution in vivo remains ill-defined. To elucidate the effects of tumor-host interactions in vivo, we purified tumor cells from 24 treatment-naive patients. Samples were obtained concurrently from blood, bone marrow, and/or LN and analyzed by gene expression profiling. We identified the LN as a key site in CLL pathogenesis. CLL cells in the LN showed up-regulation of gene signatures, indicating B-cell receptor (BCR) and nuclear factor-κB activation. Consistent with antigen-dependent BCR signaling and canonical nuclear factor-κB activation, we detected phosphorylation of SYK and IκBα, respectively. Expression of BCR target genes was stronger in clinically more aggressive CLL, indicating more effective BCR signaling in this subtype in vivo. Tumor proliferation, quantified by the expression of the E2F and c-MYC target genes and verified with Ki67 staining by flow cytometry, was highest in the LN and was correlated with clinical disease progression. These data identify the disruption of tumor microenvironment interactions and the inhibition of BCR signaling as promising therapeutic strategies in CLL. This study is registered at http://clinicaltrials.gov as NCT00019370