Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults.

Case report: aortoenteric fistula presenting as repeated hematochezia.

BACKGROUND: Aortoenteric fistula (AEF) is a rare but life-threatening condition in which expedient diagnosis is often difficult. It arises from erosion of a segment of aorta, usually an abdominal aortic aneurysm, into an adjacent portion of the gastrointestinal tract or between a vascular graft of the aorta and an adjacent portion of the gastrointestinal tract. It can present as life-threatening upper or lower gastrointestinal bleeding and is a surgical emergency that requires rapid assessment, emergency resuscitation, and definitive treatment. CASE REPORT: To present the case of an 87-year-old man diagnosed with AEF in the emergency department. A review of the literature follows the case report. CONCLUSIONS: Aortoenteric fistula is a rare diagnosis that can cause sudden life-threatening gastrointestinal bleeding.

Regional highlights in global emergency medicine development.

There are a number of notable trends in the development of EM that have been highlighted at the regional level globally. From the establishment of formal EM training as the standard of care to practice in an ED to the influence of transnational regulatory bodies and financing mechanisms on specialty development and the broad-based issues of health security that affect EM, the specialty continues to grow around the world. As practitioners in each of these regions struggle to respond effectively to the development issues and challenges presented here, they continue to advance EM as one of the more dynamic young specialties in medicine. The regions presented here are as distinctive as the people who practice our specialty; however, in many respects the highlights and challenges are universal. This recognition is perhaps what motivates the appeal for collaboration in international EM development.

Funding emergency medicine development in low- and middle-income countries.

The specialty of EM is developing rapidly throughout the world. This growth is relatively lacking in the LICs, however. The lack of resources and financing capabilities in these regions may hinder specialty development. Further growth of the specialty in these countries requires an understanding of their health priorities and the global health and development agencies that often assist these countries in supporting the health sector. Identifying health priorities in these regions that intersect with EM is crucial and may form the basis for further expansion of EM. Many potential funding opportunities exist within the governmental and private sector, but all require some familiarity with application mechanisms and project cycles. Building relationships with personnel within these agencies and countries of interest is often fundamental to successful programmatic funding.

Incidence of transient hypoxia and pulse rate reactivity during paramedic rapid sequence intubation.

STUDY OBJECTIVE: We determine the incidence of desaturation and pulse rate reactivity during paramedic rapid sequence intubation of patients with severe head injuries (Glasgow Coma Scale score