Clinical Intervention to Reduce Dietary Sugar Does Not Affect Liver Fat in Latino Youth, Regardless of PNPLA3 Genotype: A Randomized Controlled Trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) among Latinos is partially attributed to a prevalent C>G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Cross-sectional analyses in Latino children showed the association between dietary sugar and liver fat was exacerbated by GG genotype. Pediatric feeding studies show extreme sugar restriction improves liver fat, but no prior trial has examined the impact of a clinical intervention or whether effects differ by PNPLA3 genotype. OBJECTIVES: We aimed to test effects of a clinical intervention to reduce dietary sugar compared with standard dietary advice on change in liver fat, and secondary-endpoint changes in liver fibrosis, liver enzymes, and anthropometrics; and whether effects differ by PNPLA3 genotype (assessed retrospectively) in Latino youth with obesity (BMI ≥ 95th percentile). METHODS: This parallel-design trial randomly assigned participants (n = 105; mean baseline liver fat: 12.7%; mean age: 14.8 y) to control or sugar reduction (goal of ≤10% of calories from free sugar) for 12 wk. Intervention participants met with a dietitian monthly and received delivery of bottled water. Changes in liver fat, by MRI, were assessed by intervention group via general linear models. RESULTS: Mean free sugar intake decreased in intervention compared with control [11.5% to 7.3% compared with 13.9% to 10.7% (% energy), respectively; P = 0.02], but there were no significant effects on liver outcomes or anthropometrics (Pall > 0.10), and no PNPLA3 interactions (Pall > 0.10). In exploratory analyses, participants with whole-body fat mass (FM) reduction (mean ± SD: -1.9 ± 2.4 kg), irrespective of randomization, had significant reductions in liver fat compared with participants without FM reduction (median: -2.1%; IQR: -6.5% to -0.8% compared with 0.3%; IQR: -1.0% to 1.1%; P < 0.001). CONCLUSIONS: In Latino youth with obesity, a dietitian-led sugar reduction intervention did not improve liver outcomes compared with control, regardless of PNPLA3 genotype. Results suggest FM reduction is important for liver fat reduction, confirming clinical recommendations of weight loss and a healthy diet for pediatric NAFLD.This trial was registered at clinicaltrials.gov as NCT02948647.

Urban Air Pollution Nanoparticles from Los Angeles: Recently Decreased Neurotoxicity.

BACKGROUND: Air pollution is widely associated with accelerated cognitive decline at later ages and risk of Alzheimer's disease (AD). Correspondingly, rodent models demonstrate the neurotoxicity of ambient air pollution and its components. Our studies with nano-sized particulate matter (nPM) from urban Los Angeles collected since 2009 have shown pro-amyloidogenic and pro-inflammatory responses. However, recent batches of nPM have diminished induction of the glutamate receptor GluA1 subunit, Iba1, TNFα, Aß42 peptide, and white matter damage. The same methods, materials, and mouse genotypes were used throughout. OBJECTIVE: Expand the nPM batch comparisons and evaluate archived brain samples to identify the earliest change in nPM potency. METHODS: Batches of nPM were analyzed by in vitro cell assays for NF-κB and Nrf2 induction for comparison with in vivo responses of mouse brain regions from mice exposed to these batches, analyzed by PCR and western blot. RESULTS: Five older nPM batches (2009-2017) and four recent nPM batches (2018, 2019) for NF-κB and Nrf2 induction showed declines in nPM potency after 2017 that paralleled declines of in vivo activity from independent exposures in different years. CONCLUSION: Transcription-based in vitro assays of nPM corresponded to the loss of in vivo potency for inflammatory and oxidative responses. These recent decreases of nPM neurotoxicity give a rationale for evaluating possible benefits to the risk of dementia and stroke in Los Angeles populations.

Patient Satisfaction and Trust in Telemedicine During the COVID-19 Pandemic: Retrospective Observational Study.

BACKGROUND: Los Angeles County is a hub for COVID-19 cases in the United States. Academic health centers rapidly deployed and leveraged telemedicine to permit uninterrupted care of patients. Telemedicine enjoys high patient satisfaction, yet little is known about the level of satisfaction during a crisis and to what extent patient- or visit-related factors and trust play when in-person visits are eliminated. OBJECTIVE: The aim of this study is to examine correlates of patients' satisfaction with a telemedicine visit. METHODS: In this retrospective observational study conducted in our single-institution, urban, academic medical center in Los Angeles, internal medicine patients aged ≥18 years who completed a telemedicine visit between March 10th and April 17th, 2020, were invited for a survey (n=1624). Measures included patient demographics, degree of interpersonal trust in patient-physician relationships (using the Trust in Physician Scale), and visit-related concerns. Statistical analysis used descriptive statistics, Spearman rank-order correlation, and linear and ordinal logistic regression. RESULTS: Of 1624 telemedicine visits conducted during this period, 368 (22.7%) patients participated in the survey. Across the study, respondents were very satisfied (173/365, 47.4%) or satisfied (n=129, 35.3%) with their telemedicine visit. Higher physician trust was associated with higher patient satisfaction (Spearman correlation r=0.51, P<.001). Visit-related factors with statistically significant correlation with Trust in Physician score were technical issues with the telemedicine visit (r=-0.16), concerns about privacy (r=-0.19), concerns about cost (r=-0.23), satisfaction with telemedicine convenience (r=0.41), and amount of time spent (r=0.47; all P<.01). Visit-related factors associated with patients' satisfaction included fewer technical issues (P<.001), less concern about privacy (P<.001) or cost (P=.02), and successful face-to-face video (P<.001). The only patient variable with a significant positive association was income and level of trust in physician (r=0.18, P<.001). Younger age was associated with higher satisfaction with the telemedicine visit (P=.005). CONCLUSIONS: There have been calls for redesigning primary care after the COVID-19 pandemic and for the widespread adoption of telemedicine. Patients' satisfaction with telemedicine during the COVID-19 pandemic is high. Their satisfaction is shaped by the degree of trust in physician and visit-related factors more so than patient factors. This has widespread implications for outpatient practices and further research into visit-related factors and the patient-provider connection over telemedicine is needed.

Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women.

Metabolic profile and ApoE4 genotype have effects on coronary heart disease. We examined the interaction between these factors on subclinical atherosclerosis in postmenopausal women from the Early versus Late Intervention Trial with Estradiol (n = 497). Based on nine metabolic biomarkers (fasting blood glucose, insulin sensitivity, ketones, triglycerides, high-density lipoprotein, low-density lipoprotein, hemoglobin A1c, and blood pressure), K-means clustering categorized women into three distinct phenotypes: healthy, high blood pressure, and poor metabolic. ApoE4 genotype was classified as either ApoE4+ or ApoE4-. General linear models tested whether the cross-sectional association between metabolic phenotypes and common carotid intima media thickness (CIMT) differed by ApoE4 genotype. Mixed effects linear models evaluated the modifying role of ApoE4 genotype on the association of metabolic phenotype with CIMT progression over a median follow-up of 4.8 years. In cross-sectional analysis, ApoE4+ women with poor metabolic phenotype had the highest CIMT compared with all other groups. In ApoE4- women, CIMT was significantly lower in those classified as healthy compared with high blood pressure phenotype (p = 0.004). In ApoE4+ women, CIMT was significantly higher in those with poor metabolic phenotype compared with healthy (p = 0.0003) and high blood pressure (p = 0.001) phenotypes. These results indicate that metabolic phenotype had a negative effect on CIMT in women with ApoE4+ but not ApoE4- (interaction p = 0.001). These effects were not observed on CIMT progression in longitudinal analysis. In conclusion, ApoE4+ women are more likely to have higher levels of subclinical atherosclerosis if their metabolic phenotype is poor compared with ApoE4+ women without poor metabolic profile and ApoE4- women.

Drug-Induced Sleep Endoscopy Findings in Supine vs Nonsupine Body Positions in Positional and Nonpositional Obstructive Sleep Apnea.

Importance: The anatomic mechanisms underlying positional vs nonpositional obstructive sleep apnea (OSA) are poorly understood and may inform treatment decisions. Objective: To examine drug-induced sleep endoscopy (DISE) findings in the supine vs nonsupine body positions in positional and nonpositional obstructive sleep apnea. Design, Setting, and Participants: A cross-sectional study of 65 consecutive eligible adults with OSA undergoing DISE without marked tonsillar hypertrophy, including 39 with positional OSA (POSA) and 26 with nonpositional OSA (N-POSA) was conducted in a sleep surgery practice at a tertiary academic medical center. Exposures: Drug-induced sleep endoscopy performed in the supine vs nonsupine body position. Main Outcomes and Measures: Drug-induced sleep endoscopy findings were scored separately for the supine and lateral body positions using the VOTE classification (velum, oroparyngeal lateral walls, tongue, epiglotis) and with identification of a single primary structure contributing to airway obstruction. Velum-related obstruction was separated into anteroposterior and lateral components. Results: The 65 study participants had a mean (SD) age of 52.4 (11.7) years, and 55 (84.6) were men. Mean (SD) body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) was 27.2 (3.1), with only 9 (14%) of 65 participants having a BMI greater than 30. The supine body position was associated with greater odds of anteroposterior velum- (odds ratio [OR], 7.28; 95% CI, 3.53-15.01), tongue- (OR, 29.4; 95% CI, 12.1-71.5), and epiglottis-related (OR, 11.0; 95% CI, 1.3-92.7) obstruction in the entire cohort, with similar findings in the POSA and N-POSA subgroups. The supine body position was associated with a lower odds of oropharyngeal lateral wall-related (OR, 0.22; 95% CI, 0.07-0.70) obstruction in the N-POSA subgroup, whereas there was no increase in the overall sample or the POSA subgroup. The oropharyngeal lateral walls were a common primary structure causing obstruction, especially in the lateral body position. Conclusions and Relevance: In a study population of primarily nonobese adults, DISE findings differed based on body position, generally corresponding to gravitational factors. Treatments that address velum- and tongue-related obstruction successfully may be more effective in the POSA population.