The Indian Health Service and American Indian/Alaska Native Health Outcomes.

The Indian Health Service (IHS) has made huge strides in narrowing health disparities between American Indian and Alaska Native (AI/AN) populations and other racial and ethnic groups. Yet, health disparities experienced by AI/AN people persist, with deep historical roots combined with present-day challenges. Here we review the history of the IHS from colonization to the present-day system, highlight persistent disparities in AI/AN health and health care, and discuss six key present-day challenges: inadequate funding, limited human resources, challenges associated with transitioning services from federal to Tribal control through contracting and compacting, evolving federal and state programs, the need for culturally sensitive services, and the promise and challenges of health technology.

Simultaneous measurement of biochemical phenotypes and gene expression in single cells.

Methods to measure heterogeneity among cells are rapidly transforming our understanding of biology but are currently limited to molecular abundance measurements. We developed an approach to simultaneously measure biochemical activities and mRNA abundance in single cells to understand the heterogeneity of DNA repair activities across thousands of human lymphocytes, identifying known and novel cell-type-specific DNA repair phenotypes.

Cardiovascular Disease Burden and Outcomes Among American Indian and Alaska Native Medicare Beneficiaries.

Importance: American Indian and Alaska Native persons face significant health disparities; however, data regarding the burden of cardiovascular disease in the current era is limited. Objective: To determine the incidence and prevalence of cardiovascular disease, the burden of comorbid conditions, including cardiovascular disease risk factors, and associated mortality among American Indian and Alaska Native patients with Medicare insurance. Design, Setting, and Participants: This was a population-based cohort study conducted from January 2015 to December 2019 using Medicare administrative data. Participants included American Indian and Alaska Native Medicare beneficiaries 65 years and older enrolled in both Medicare part A and B fee-for-service Medicare. Statistical analyses were performed from November 2022 to April 2023. Main Outcomes and Measures: The annual incidence, prevalence, and mortality associated with coronary artery disease (CAD), heart failure (HF), atrial fibrillation/flutter (AF), and cerebrovascular disease (stroke or transient ischemic attack [TIA]). Results: Among 220 598 American Indian and Alaska Native Medicare beneficiaries, the median (IQR) age was 72.5 (68.5-79.0) years, 127 402 were female (57.8%), 78 438 (38.8%) came from communities in the most economically distressed quintile in the Distressed Communities Index. In the cohort, 44.8% of patients (98 833) were diagnosed with diabetes, 61.3% (135 124) were diagnosed with hyperlipidemia, and 72.2% (159 365) were diagnosed with hypertension during the study period. The prevalence of CAD was 38.6% (61 125 patients) in 2015 and 36.7% (68 130 patients) in 2019 (P < .001). The incidence of acute myocardial infarction increased from 6.9 per 1000 person-years in 2015 to 7.7 per 1000 patient-years in 2019 (percentage change, 4.79%; P < .001). The prevalence of HF was 22.9% (36 288 patients) in 2015 and 21.4% (39 857 patients) in 2019 (P < .001). The incidence of HF increased from 26.1 per 1000 person-years in 2015 to 27.0 per 1000 person-years in 2019 (percentage change, 4.08%; P < .001). AF had a stable prevalence of 9% during the study period (2015: 9.4% [14 899 patients] vs 2019: 9.3% [25 175 patients]). The incidence of stroke or TIA decreased slightly throughout the study period (12.7 per 1000 person-years in 2015 and 12.1 per 1000 person-years in 2019; percentage change, 5.08; P = .004). Fifty percent of patients (110 244) had at least 1 severe cardiovascular condition (CAD, HF, AF, or cerebrovascular disease), and the overall mortality rate for the cohort was 19.8% (43 589 patients). Conclusions and Relevance: In this large cohort study of American Indian and Alaska Native patients with Medicare insurance in the US, results suggest a significant burden of cardiovascular disease and cardiometabolic risk factors. These results highlight the critical need for future efforts to prioritize the cardiovascular health of this population.

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma.

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

Case report of a paraganglioma arising from a mature cystic teratoma of the ovary.

Paragangliomas are rare neuroendocrine neoplasms derived from sympathetic or parasympathetic paraganglia and have the ability to secrete catecholamines. We present the case of a 37-year-old asymptomatic female who underwent right ovarian cystectomy for a mature cystic teratoma and was found to have an intra-tumoral paraganglioma. More research is needed to determine metastatic potential as well as the likelihood of recurrence of these unique neoplasms.