Our goal was to evaluate the safety and toxicity of combining a PARP inhibitor, olaparib, with cetuximab and fractionated intensity-modulated radiotherapy for patients with locally advanced head and neck cancer and heavy smoking histories. Patients with ≥10 packs/year history of smoking were treated with olaparib at doses ranging from 25-200 mg orally twice daily beginning approximately 10 days prior to initiation of and with concurrent radiation (69.3 Gy in 33 fractions) using a time-to-event continual reassessment method model. Cetuximab was administered starting approximately 5 days prior to radiation per standard of care. A total of 16 patients were entered onto the study, with 15 evaluable for acute toxicity. The most common treatment-related grade 3-4 side effects were radiation dermatitis and mucositis (38% and 69%, respectively). The MTD was determined to be 50 mg orally twice daily, but the recommended phase II dose was deemed to be 25 mg orally twice daily. At a median follow-up of 26 months, the actuarial median overall survival was 37 months, but was not reached for other endpoints. Two-year overall survival, progression-free survival, local control, and distant control rates were 72%, 63%, 72%, and 79%, respectively. Patients who continued to smoke during therapy experienced higher recurrence rates. and were identified as potential correlatives of response on gene amplification and mutational analysis. Olaparib at 25 mg orally twice daily with concurrent cetuximab and radiation was well tolerated with reduced dermatitis within the radiation field. Response rates were promising for this high-risk population. .

Objectives: Diabetes and depression are commonly present in the same individuals, suggesting the possibility of underlying shared physiological processes. Inflammation, as assessed with the biomarker C-reactive protein (CRP), has not consistently explained the observed relationship between diabetes and depression, although both are associated with inflammation and share proposed inflammatory mechanisms. Central adiposity has also been associated with both conditions, potentially by causing increased inflammation. This study uses the World Health Organization's Study on global AGEing and adult health (SAGE) Mexico Wave 1 biomarker data (n = 1831) to evaluate if inflammation and central adiposity mediate the relationship between depression and diabetes. Methods: Depression was estimated using a behavior-based diagnostic algorithm, inflammation using venous dried blood spot (DBS) CRP, central adiposity using waist-to-height ratio (WHtR), and uncontrolled diabetes using venous DBS-glycated hemoglobin (HbA1c). Results: The association between depression and uncontrolled diabetes was partially mediated by CRP before but not after WHtR was considered. When WHtR was added to the model, it partially mediated the relationship between diabetes and depression while fully mediating the relationship between depression and CRP. Conclusions: These findings suggest that central adiposity may be a more significant mediator between diabetes and depression than inflammation and account for the relationship between these disorders and inflammation. Depression may cause an increase in central adiposity, which then may lead to diabetes, but the increase in known systemic inflammatory pathways caused by central adiposity may not be the key pathological mechanism.

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Despite advances in cancer medicine and research, invasive and potentially risky procedures such as biopsies, venous blood tests, imaging, colonoscopy, and pap smear tests are still primarily used for screening, staging, and assessing response to therapy. The development and interdisciplinary use of biomarkers from urine, feces, saliva, scent, and capillary blood collected with minimally invasive methods represents a potential opportunity for integration with biomarker analysis for cancers, both in clinical practice (e.g., in screening, treatment, and disease monitoring, and improved quality of life for patients) and population-based research (e.g., in epidemiology/public health, studies of social and environmental determinants, and evolutionary medicine). In this article, we review the scientific rationale, benefits, challenges, and potential opportunities for measuring cancer-related biomarkers in samples collected through minimally invasive methods.

Objective Anemia is an important global health challenge. We investigate anemia prevalence among Indigenous Shuar of Ecuador to expand our understanding of population‐level variation, and to test hypotheses about how anemia variation is related to age, sex, and market integration. Methods Hemoglobin levels were measured in a total sample of 1650 Shuar participants (ages 6 months to 86 years) from 46 communities between 2008 and 2017 to compare anemia prevalence across regions characterized by different levels of market integration. Results Shuar anemia rates among children under 15 years (12.2%), adult women (10.5%), and adult men (5.3%) were less than half of those previously documented in other neo‐tropical Indigenous populations. Anemia prevalence did not vary between more traditional and market integrated communities (OR = 0.47, p = .52). However, anemia was negatively associated with body mass index (OR = 0.47, p = .002). Conclusions Compared to other South American Indigenous populations, anemia prevalence is relatively low among Shuar of Ecuador and invariant with market integration. Understanding this pattern can provide valuable insights into anemia prevention among at‐risk populations.