Alexander L. Chin

Diversity and disparity in dementia: the impact of ethnoracial differences in Alzheimer disease.

Debate exists regarding differences in the prevalence of Alzheimer disease (AD) in African Americans and Hispanics in the United States, with some evidence suggesting that the prevalence of AD may be considerably higher in these groups than in non-Hispanic whites. Despite this possible disparity, patients of minority ethnoracial groups often receive delayed diagnosis or inadequate treatment for dementia. This review investigates these disparities by conceptualizing the dementia disease process as a product of both biological and cultural factors. Ethnoracial differences in biological risk factors, such as genetics and cardiovascular disease, may help to explain disparities in the incidence and prevalence of AD, whereas race-specific cultural factors may impact diagnosis and treatment. Cultural factors include differences in perceptions about what is normal aging and what is not, lack of adequate access to medical care, and issues of trust between minority groups and the medical establishment. The diagnosis of AD in diverse populations may also be complicated by racial biases inherent in cognitive screening tools widely used by clinicians, but controlling for literacy level or using savings scores in psychometric analyses has the potential to mitigate these biases. We also suggest that emerging biomarker-based diagnostic tools may be useful in further characterizing diverse populations with AD. Recognizing the gap in communication that exists between minority communities and the medical research community, we propose that education and outreach are a critical next step in the effort to understand AD as it relates to diverse populations.

The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion

Enterochromaffin (EC) cells of the diffuse neuroendocrine cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitivity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98-99%) FACS-sorted normal and IBD human EC cells and neoplastic EC cells (KRJ-I) were studied. IBD-EC cells and KRJ-I overexpressed ADORA2B. NECA, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS1754 inhibited, 5-HT release (EC50 = 1.8 × 10-6 M; IC50 = 3.7 × 10-8 M), which was associated with corresponding alterations in intracellular cAMP levels and pCREB (Ser133). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMAT₁ (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tph1 and VMAT₁ transcription was regulated by PKA/MAPK and PI₃K-mediated signaling. Normal and IBD-EC cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC cell function are necessary for understanding its role as a mechanosensory cell and to facilitate the development of agents that can selectively target cell function in EC cell-associated disease.

Feasibility and limitations of bulk density assignment in MRI for head and neck IMRT treatment planning

Head and neck cancers centered at the base of skull are better visualized on MRI than on CT. The purpose of this investigation was to investigate the accuracy of bulk density assignment in head and neck intensity‐modulated radiation therapy (IMRT) treatment plan optimization. Our study investigates dose calculation differences between density‐assigned MRI and CT, and identifies potential limitations related to dental implants and MRI geometrical distortion in the framework of MRI‐only‐based treatment planning. Bulk density assignment was performed and applied onto MRI to generate three MRI image sets with increasing levels of heterogeneity for seven patients: 1) MRIW: all water‐equivalent; 2) MRIW + B: included bone with density of 1.53 g/cm3; and 3) MRIW + B + A: included bone and air. Using identical planning and optimization parameters, MRI‐based IMRT plans were generated and compared to corresponding, forward‐calculated, CT‐based plans on the basis of target coverage, isodose distributions, and dose‐volume histograms (DVHs). Phantom studies were performed to assess the magnitude and spatial dependence of MRI geometrical distortion. MRIW‐based dose calculations overestimated target coverage by 16.1%. Segmentation of bone reduced differences to within 2% of the coverage area on the CT‐based plan. Further segmentation of air improved conformity near air–tissue interfaces. Dental artifacts caused substantial target coverage overestimation even on MRIW + B + A. Geometrical distortion was less than 1 mm in an imaging volume 20 × 20 × 20 cm3 around scanner isocenter, but up to 4 mm at 17 cm lateral to isocenter. Bulk density assignment in the framework of MRI‐only IMRT head and neck treatment planning is a feasible method with certain limitations. Bone and teeth account for the majority of density heterogeneity effects. While soft tissue is well visualized on MRI compared to CT, dental implants may not be visible on MRI and must be identified by other means and assigned appropriate density for accurate dose calculation. Far off‐center geometrical distortion of the body contour near the shoulder region is a potential source of dose calculation inaccuracy. PACS numbers: 87.61.‐c, 87.55.‐D

Quality, and not just quantity, of education accounts for differences in psychometric performance between African Americans and White Non-Hispanics with Alzheimer’s disease

The effect of race on cognitive test performance in the evaluation of Alzheimers disease (AD) remains controversial. One factor that may contribute substantially to differences in cognitive test performance in diverse populations is education. The current study examined the extent to which quality of education, even after controlling for formal years of education, accounts for differences in cognitive performance between African Americans and White Non-Hispanics (WNHs). The retrospective cohort included 244 patients diagnosed with AD who self-identified as African Americans (n = 51) or WNHs (n = 193). The Wechsler Test of Adult Reading (WTAR) was used as an estimate of quality of education. In an analysis that controlled for traditional demographics, including age, sex, and years of formal education, African Americans scored significantly lower than WNHs on the Mini-Mental State Examination, as well as on neuropsychological tests of memory, attention, and language. However, after also adjusting for reading level, all previously observed differences were significantly attenuated. The attenuating effect remained even after controlling for disease severity, indicating that reading scores are not confounded by severity of dementia. These findings suggest that quality, and not just quantity, of education needs to be taken into account when assessing cognitive performance in African Americans with AD.

Normal Tissue Constraints for Abdominal and Thoracic Stereotactic Body Radiotherapy

Although stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has become an established standard of care for the treatment of a variety of malignancies, our understanding of normal tissue dose tolerance with extreme hypofractionation remains immature. Since Timmerman initially proposed normal tissue dose constraints for SBRT in the 2008 issue of Seminars of Radiation Oncology, experience with SBRT has grown, and more long-term clinical outcome data have been reported. This article reviews the modern toxicity literature and provides updated clinically practical and useful recommendations of SBRT dose constraints for extracranial sites. We focus on the major organs of the thoracic and upper abdomen, specifically the liver and the lung.

Cost-effectiveness of radiation and chemotherapy for high-risk low-grade glioma

Background The addition of procarbazine, lomustine, vincristine (PCV) chemotherapy to radiotherapy (RT) for patients with high-risk (≥40 y old or subtotally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy. Methods A decision tree with an integrated 3-state Markov model was created to follow patients with high-risk LGG after surgery treated with RT versus RT+PCV. Patients existed in one of 3 health states: stable, progressive, or dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the health care perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters. Results Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs 5.17 for RT alone) at an incremental cost of

Survival impact of postoperative radiotherapy timing in pediatric and adolescent medulloblastoma

48635 (

Rising rates of bilateral mastectomy with reconstruction following neoadjuvant chemotherapy: Breast surgery after neoadjuvant chemotherapy

188234 for RT+PCV vs

Prognostic Value of Pretreatment FDG-PET Parameters in High-dose Image-guided Radiotherapy for Oligometastatic Non–Small-cell Lung Cancer

139598 for RT alone), resulting in an incremental cost-effectiveness ratio of

The role of bone marrow and spleen irradiation in the development of acute hematologic toxicity during chemoradiation for esophageal cancer

10186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of