Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index at Diagnosis Is Associated with All-Cause Mortality during Follow-Up in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and Objectives: The purpose of this study was to investigate whether a new index related to chronic liver disease, the alcoholic liver disease/nonalcoholic fatty liver disease index (ANI) at diagnosis, is associated with all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: In this study, we included 270 patients with AAV. ANI was calculated using the following equation: ANI = -58.5 + 0.637 (adjusted mean corpuscular volume) + 3.91 (adjusted aspartate transaminase/alanine transaminase) - 0.406 (body mass index) + 6.35 (if male sex). All-cause mortality was defined as death from any cause during follow-up. Results: The median age of the 270 patients with AAV was 61.0 years (34.4% male and 66.6% female). The median ANI was significantly higher in deceased patients than in surviving patients. In the receiver operating characteristic curve analysis, ANI at diagnosis exhibited a statistically significant area under the curve for all-cause mortality during follow-up, and its cut-off was determined to be -0.59. Patients with ANI at diagnosis ≥ -0.59 exhibited a significantly higher risk for all-cause mortality and a significantly lower cumulative patient survival rate than those without. In the multivariable Cox analysis, ANI at diagnosis ≥ -0.59, together with age at diagnosis, was independently associated with all-cause mortality. Conclusions: This study is the first to demonstrate the predictive potential of ANI at diagnosis for all-cause mortality during follow-up in AAV patients without significant chronic liver diseases.

First-year cumulative myeloperoxidase-ANCA titres are associated with all-cause mortality in patients with microscopic polyangiitis.

OBJECTIVES: We investigated whether first-year cumulative myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3 (PR3)-ANCA titres were associated with all-cause mortality and relapse during follow-up in patients with microscopic polyangiitis (MPA) and granMETHODS: Altogether, 74 patients with MPA and 40 with GPA were included in this study. Their clinical data at diagnosis were collected. First-year cumulative ANCA titres were defined as the area under the curve (AUC) of ANCA titres during the first year after MPA or GPA diagnosis, which was obtained using the trapezoidal rule. All-cause mortality and relapse were considered poor outcomes of MPA and GPA. RESULTS: The median ages of patients with MPA and GPA were 65.5 and 60.5 years, respectively. No significant correlation was observed between ANCA titres at diagnosis and concurrent MPA and GPA activity or the inflammatory burden. First-year cumulative MPO-ANCA titres exhibited a significant AUC for all-cause mortality during follow-up in patients with MPA. The optimal cut-off of first-year cumulative MPO-ANCA titres for all-cause mortality was determined as 720.8 IU/mL using receiver operating characteristic curve analysis. MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly higher risk for all-cause mortality than those without (relative risk 13.250). Additionally, MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSIONS: This is the first study to demonstrate the association between first-year cumulative MPO-ANCA titres and all-cause mortality during follow-up in patients with MPA.

From engineered heart tissue to cardiac organoid.

The advent of human pluripotent stem cells (hPSCs) presented a new paradigm to employ hPSC-derived cardiomyocytes (hPSC-CMs) in drug screening and disease modeling. However, hPSC-CMs differentiated in conventional two-dimensional systems are structurally and functionally immature. Moreover, these differentiation systems generate predominantly one type of cell. Since the heart includes not only CMs but other cell types, such monolayer cultures have limitations in simulating the native heart. Accordingly, three-dimensional (3D) cardiac tissues have been developed as a better platform by including various cardiac cell types and extracellular matrices. Two advances were made for 3D cardiac tissue generation. One type is engineered heart tissues (EHTs), which are constructed by 3D cell culture of cardiac cells using an engineering technology. This system provides a convenient real-time analysis of cardiac function, as well as a precise control of the input/output flow and mechanical/electrical stimulation. The other type is cardiac organoids, which are formed through self-organization of differentiating cardiac lineage cells from hPSCs. While mature cardiac organoids are more desirable, at present only primitive forms of organoids are available. In this review, we discuss various models of hEHTs and cardiac organoids emulating the human heart, focusing on their unique features, utility, and limitations.

Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts.

Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.

Clinical Characteristics of Asymptomatic and Symptomatic Pediatric Coronavirus Disease 2019 (COVID-19): A Systematic Review.

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.

Association between family dinner and BMI in adults: data from the 2013 to 2015 Korean National Health and Nutrition Examination Survey.

OBJECTIVE: People who eat alone, which is becoming a new trend owing to the increasing proportion of one-person households in Korea, are more likely to become overweight and obese. Therefore, we investigated the association between having a dinner companion and BMI. DESIGN: A linear regression model adjusted for covariates was utilized to examine the association between having a dinner companion and BMI. Subgroup analyses were performed, stratified by age group, gender, household income, educational level and occupation. SETTING: We used the data from the Korean Health and Nutrition Examination Survey VI. Our primary independent variable was having a dinner companion while the dependent variable was BMI. SUBJECTS: In total, 13303 individuals, aged 20 years or over, were analysed. RESULTS: Compared with the solo eating group, BMI was lower in the family dinner group (ß=-0·39, P<0·01) but not in the non-family dinner group (ß=-0·06, P=0·67). The subgroup analysis revealed that the difference in BMI was most significant in young generations, such as those aged 20-29 years (ß=-1·15, P<0·01) and 30-39 years (ß=-0·78, P=0·01). CONCLUSIONS: We found that people who eat dinner alone are more likely to become overweight and obese than those who eat with their family. This association was stronger in males and young adults than their counterparts. Considering the increasing trends in the proportion of single-person households and solo eating, appropriate intervention is needed.