Prevalence of dilated mid-ascending aorta in individuals 15 years and older: In search of optimal diagnostic criteria and their effect on the burden of disease.

BACKGROUND: Controversy regarding the definition of the upper limit of normal (ULN) for dilated mid-ascending aorta (mAA) stems from variation in criteria, based on several small-sized studies with small datasets of normal subjects (DONS). The present study was carried out to demonstrate this variation in the prevalence of mAA dilation and to identify the optimal definition by creating the largest DONS. METHODS: Echocardiographic studies of patients ≥ 15 years of age performed at a large tertiary care center over 4 years (n = 49,330) were retrospectively evaluated. The leading-edge-to-leading-edge technique was used to measure the mAA in diastole. The largest-to-date DONS (n = 2334) was created, including those who were normal on medical record review, did not have any of the 28 causes of dilated aorta, and had normal echocardiograms. Because age had the strongest correlation with mAA (multivariate adjusted R2 = 0.26), as compared with sex, height, and weight, we created a new ULN based on the DONS with narrow age stratification (10-year intervals). RESULTS: The prevalence of dilated mAA varied between 17% and 23% when absolute criteria were used with sex stratification, and it varied between 6% and 11% when relative criteria (relative to age, body surface area, and sex) were used. Based on new criteria from the DONS, it was 7.6%, with a ULN of 3.07-3.64 cm in women and 3.3-3.91 cm in men. CONCLUSIONS: These data demonstrate the undesirable variation in the prevalence of dilated mAA based on prior criteria and propose a new ULN for dilated mAA.

Hypertrophic cardiomyopathy is associated with dilated sinus of Valsalva: A case-control study.

Background: We aimed to test the hypothesis that there is an association between hypertrophic cardiomyopathy and dilated aorta in a case-control, matched-design fashion. Methods: Of 65,843 studies done from November 2011 to December 2015, we found, after detailed evaluation by a single author, 153 cases of hypertrophic cardiomyopathy and 3,213 controls who were classified as normal clinically and echocardiographically. Controls were defined as normal patients referred to the echocardiography laboratory with no diagnoses and no known risk factors for dilated aorta (e.g., aortic stenosis, hypertension, aortic regurgitation). Clinical chart review showed none of the risk factors for dilated aorta, and echocardiography did not reveal any abnormalities. Of these 3,213 patients, 153 controls were matched to cases by age and sex by propensity score. Dilated aorta was defined according to clinical, Goldstein, and Lang's criteria. Results: The prevalence of a dilated sinus of Valsalva was 9 times higher in hypertrophic cardiomyopathy patients than controls (OR = 9.4, P = 0.003). The 9-fold higher prevalence in hypertrophic cardiomyopathy patients persisted after adjusting for height, weight, and aortic pathology. Association of dilated mid-ascending aorta with hypertrophic cardiomyopathy was significant after adjustment for height and body surface area but became borderline insignificant after adjusting for weight and aortic valve pathology. Conclusion: Hypertrophic cardiomyopathy appears to be associated with a dilated sinus of Valsalva, even after adjusting for height, weight, and aortic valve pathology.

Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen.

PURPOSE: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen. METHODS: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks. RESULTS: A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis. CONCLUSION: Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.

Perspective of Emergency Pediatric Nurses Triaging Pediatric Patients in the Emergency Department: A Phenomenographic Study.

INTRODUCTION: Triage, a process to determine illness severity, is implemented by emergency nurses to prioritize treatment and provide care for a maximum number of patients using limited resources. The competency of emergency nurses and a highly reliable triage are crucial for the provision of emergency care. Pediatric patients are different from adult patients in certain aspects, such as growth-phase characteristics, communication ability, and the onset of disease; these aspects often pose challenges during their primary triage. This study explored how emergency nurses triage pediatric patients using the Korean Triage and Acuity Scale. METHODS: Eleven emergency nurses (N = 11) working in the pediatric emergency department of a university hospital in Seoul, South Korea, were recruited using purposive sampling methods. Phenomenography was used to investigate the strategies by which these nurses use the Korean Triage and Acuity Scale to triage pediatric patients. RESULTS: The findings comprised 2 descriptive categories: 6 approaches on how to triage patients (categories of how) and 3 strategies (categories of what) used by pediatric emergency nurses to triage pediatric patients with the Korean Triage and Acuity Scale. DISCUSSION: The experience and proficiency of emergency nurses are essential factors for the effective triage of pediatric patients. Our findings qualitatively elucidate different ways of understanding pediatric triage and indicate the need for pediatric triage education programs.

Refining the upper limit of normal for the ascending aorta: In search of optimal criteria -- a large database study of normal individuals.

OBJECTIVES: The cutoff for dilated mid-ascending aorta (mAA) is controversial and has several definitions. The present study was carried out to determine the prevalence of mAA dilation based on published definitions and to identify the optimal cutoff. METHODS: Echocardiographic studies of patients >15 years of age performed at a large tertiary care center over 4 years, n = 49,330, were retrospectively evaluated. Leading-edge-to-leading-edge technique was used to measure the mAA in diastole. Several cutoff criteria were included. In addition, we defined normals in our database as those who, after 28 causes of dilated aorta were excluded, were normal both clinically and echocardiographically (n = 2334). RESULTS: The mean age was 64.2 ± 17.1 years, and 31.5% were men. The prevalence of dilated mAA based on absolute criteria with sex stratification varied between 17% and 23% and based on relative criteria (to age, body surface area, and sex) varied between 6% and 11%. It further decreased to 7.6% on the addition of narrow age stratification (10 year intervals) performed on normals in our database. The multivariate adjusted R2 (for variation in mAA diameter) was 0.25 for age, decreasing to 0.12 for weight and 0.07 for sex and height. CONCLUSIONS: The lowest prevalence of 7.6% probably represents the optimal cutoff for dilated mAA because it includes age, which explains most of the variation in mAA, in narrow (10 year) intervals only performed in our normals, which represents the largest sample size to date.

Higher Levels of Fibrosis in a Cohort of Veterans with Chronic Viral Hepatitis are Associated with Extrahepatic Cancers.

BACKGROUND AND AIMS: An estimated 2.4 million Americans, including more than 150,000 veterans, are chronically infected with hepatitis C virus (HCV). HCV is estimated to cause roughly 25% of all hepatocellular carcinoma. Although its mechanism is unknown, developing evidence suggests that chronic HCV infection is also associated with the development of extrahepatic cancers (EHCs). This paper aims to assess the relationship of hepatic fibrosis and chronic HCV with the risk of developing EHC. METHODS: We conducted a single-center retrospective chart review of 1541 patients linked to the hepatitis clinic at the Veterans Affairs (VA) Maryland Health Care System who underwent transient elastography for evaluation and management of liver disease from 2014 to 2018. Liver fibrosis was measured using ultrasound and transient elastography. Extrahepatic cancer and site was identified by a retrospective chart review. RESULTS: In adjusted analysis of EHCs, advanced age (OR: 1.97, 95% CI: 1.30-3.04), and higher measured stiffness (OR 2.19, 95% CI: 1.32-3.64) were associated with an increased likelihood of developing EHC, controlling for HBV infection, HCV exposure, heavy alcohol use, and body mass index. CONCLUSIONS: We observed a significant association between increasing age and increasing levels of liver fibrosis with increased risk of EHC, notably prostate, head and neck squamous cell, lung, and hematologic cancers.

Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients.

PURPOSE: Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. PATIENTS AND METHODS: We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. RESULTS: This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. CONCLUSION: These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

Circadian rhythms in urinary functions: possible roles of circadian clocks?

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.