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While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV−) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10 + LDGs were significantly decreased in PLWH. In addition, the CD16 Lo LDG subsets were enriched in PLWH, compared to HIV− group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH.

Background As a major risk factor for cardiovascular and cerebrovascular disease (CVD), hypertension affects 33% of U.S. adults. Relative to other US races and ethnicities, Native Hawaiians have a high prevalence of hypertension and are 3 to 4 times more likely to have CVD. Effective, culturally-relevant interventions are needed to address CVD risk in this population. Investigators of the Kā-HOLO Project developed a study design to test the efficacy of an intervention that uses hula, a traditional Hawaiian dance, to increase physical activity and reduce CVD risk. Methods A 2-arm randomized controlled trial with a wait-list control design will be implemented to test a 6-month intervention based on hula to manage blood pressure and reduce CVD risk in 250 adult Native Hawaiians with diagnosed hypertension. Half of the sample will be randomized to each arm, stratified across multiple study sites. Primary outcomes are reduction in systolic blood pressure and improvement in CVD risk as measured by the Framingham Risk Score. Other psychosocial and sociocultural measures will be included to determine mediators of intervention effects on primary outcomes. Assessments will be conducted at baseline, 3 months, and 6 months for all participants, and at 12 months for intervention participants only. Discussion This trial will elucidate the efficacy of a novel hypertension management program designed to reduce CVD risk in an indigenous population by using a cultural dance form as its physical activity component. The results of this culturally-based intervention will have implications for other indigenous populations globally and will offer a sustainable, culturally-relevant means of addressing CVD disparities. Trial registration ClinicalTrials.gov: NCT02620709 , registration date November 23, 2015.

Rates of insulin resistance are increased in HIV-infected patients on stable antiretroviral therapy (ART). Such increase may partially be due to HIV-induced immune dysregulation involving monocytes (MO) and its subsets. Cross-sectional analysis of 141 HIV-infected subjects age ≥ 40 years on stable ART. Homeostatic model assessment-insulin resistance (HOMA-IR) and rates of metabolic syndrome were calculated. Subjects were classified by fasting glucose and oral glucose tolerance test (OGTT) into clinical diabetes categories. Multi-parametric flow cytometry was used to determine MO subset percentages: [classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)), and a recently identified fourth (CD14(low/+)CD16(-)) 'transitional' MO subset] and percentage of activated (CD38(+)HLA-DR(+)) CD8 T cells. Absolute levels of cells were calculated using clinical CBC and T cell subset data. Multiple plasma soluble biomarkers were assessed by Luminex technology. Median age 50 years, CD4 count (percent) 505 cells/µL (29%), and 89% male. Total MO (r=-0.23, p=0.006) and classical and non-classical MO subsets correlated negatively with CD4 percent. No correlations were seen with CD4 count as absolute values. Log-total MO and log-classical MO predicted HOMA-IR independently of HIV immuno-virologic and diabetes risk factors (β=0.42, p=0.02 and β=0.35, p=0.02, respectively) and were increased in subjects with metabolic syndrome (p=0.03 and p=0.05 respectively). Total and/or subset MO levels correlated with multiple soluble plasma biomarkers including CRP, IL-6, MMP-9, MPO, SAA, SAP and tPAI-1, with tPAI-1 independently predicting HOMA-IR (β=0.74, p<0.001). MO levels increase with worsening HIV immune dysregulation as assessed by CD4 percent. CD4 percent may provide additional information about MO and metabolic risk in this population beyond absolute values. MO, and specifically classical MO, may contribute to insulin resistance and metabolic syndrome during chronic HIV infection. Multiple soluble plasma biomarkers including tPAI-1 increase with increase in MO. Levels of tPAI-1 independently predict the development of insulin resistance.

Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007–2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

The true extent of racial and ethnic disparities in COVID-19 hospitalizations may be hidden by misclassification of race and ethnicity. This study aimed to quantify this inaccuracy in a hospital's electronic medical record (EMR) against the gold standard of self-identification and then project data onto state-level COVID-19 hospitalizations by self-identified race and ethnicity. To identify misclassification of race and ethnicity in the EMRs of a hospital in Honolulu, Hawaii, research and quality improvement staff members surveyed all available patients (N = 847) in 5 cohorts in 2007, 2008, 2010, 2013, and 2020 at randomly selected hospital and ambulatory units. The survey asked patients to self-identify up to 12 races and ethnicities. We compared these data with data from EMRs. We then estimated the number of COVID-19 hospitalizations by projecting racial misclassifications onto publicly available data. We determined significant differences via simulation-constructed medians and 95% CIs. EMR-based and self-identified race and ethnicity were the same in 86.5% of the sample. Native Hawaiians (79.2%) were significantly less likely than non-Native Hawaiians (89.4%) to be correctly classified on initial analysis; this difference was driven by Native Hawaiians being more likely than non-Native Hawaiians to be multiracial (93.4% vs 30.3%). When restricted to multiracial patients only, we found no significant difference in accuracy (P = .32). The number of COVID-19-related hospitalizations was 8.7% higher among Native Hawaiians and 3.9% higher among Pacific Islanders when we projected self-identified race and ethnicity rather than using EMR data. Using self-identified rather than hospital EMR data on race and ethnicity may uncover further disparities in COVID-19 hospitalizations.

Seemingly entrenched on the extremes of two sides, it was hard for our clinicians to find common ground. [...]discussions on the merits of hydroxychloroquine quickly shifted to disagreement on the role of physician autonomy vis-à-vis the broader professional community, the meaning of \"evidence-based,\" the obligations of physicians to their patients, and the ethics of randomized controlled trials during pandemics. [...]we proceeded with our studies, basing our protocol on the standard WHO template and our inclusion/exclusion criteria and treatment regimen on the published literature. [...]it is somewhat enlightening, and slightly embarrassing, that our early clinical trials were more valuable and impactful to us—my institution, my colleagues—than to the larger scientific community.

See PDF.] A thrombus “squeezing” through a patent foramen ovale two-dimensional transesophageal echocardiography (mid-esophageal bicaval view) revealed a large (10 mm × 5 mm) mass on the right atrial side of the interatrial septum near the fossa ovalis, with a density on the adjacent left atrial side, likely reflecting a thrombus in transit that is “squeezing” through a patent foramen ovale (arrow) Author contributions Dr. Nakagawa contributed to the study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content. Dr. Seto contributed to acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content and study supervision. Ethical Approval Approval was obtained from the Queen’s Medical Center (QMC) Research and Institutional Review Committee to conduct this case report.

Food insecurity is a social determinant of health and is increasingly recognized as a risk factor for hypertension. Native Hawaiians bear a disproportionate burden of hypertension and known risk factors. Despite this, the relative effects of food insecurity and financial instability on blood pressure have yet to be investigated in this population. This study examines the relative effects of food insecurity and financial instability on blood pressure, controlling for potential confounders in a multiethnic sample. Participants (n = 124) were recruited from a U.S. Department of Agriculture-funded study called the Children’s Healthy Living Center of Excellence. Biometrics (i.e., blood pressure, weight, and height) were measured. Demographics, physical activity, diet, psychosocial variables, food insecurity, and financial instability were assessed via self-report questionnaires. Hierarchical linear regression models were conducted. Model 1, which included sociodemographic variables and known biological risk factors, explained a small but significant amount of variance in systolic blood pressure. Model 2 added physical activity and daily intake of fruit, fiber, and whole grains, significantly improving the model. Model 3 added financial instability and food insecurity, further improving the model (R2 = 0.37, F = 2.67, p = 0.031). Food insecurity, female sex, and BMI were significantly and independently associated with increased systolic blood pressure. These results suggest a direct relationship between food insecurity and systolic blood pressure, which persisted after controlling for physical activity, consumption of fruits, fiber, and whole grains, and BMI. Efforts to reduce food insecurity, particularly among Native Hawaiians, may help reduce hypertension in this high-risk population.

Abstract Context Nonalcoholic fatty liver disease, renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common cause of chronic liver disease with an estimated worldwide prevalence of 30.1% while clinical practice observations reflect a disproportionately lower prevalence of 1.9%, indicating a condition that is underrecognized in clinical care settings. Screening for MASLD is rarely performed, and little is known about the prevalence in Hawai’i. Objective This pilot aims to develop an understanding of the prevalence and factors associated with MASLD in Hawai’i's adolescent and young adult (AYA) population. Design/Methods Cross-sectional observational pilot study: We used Fibroscan®—liver ultrasonographic vibration-controlled transient elastography (VCTE) to identify MASLD based on controlled attenuation parameter (CAP) scores ≥238 (dB/m) and collected biometric, anthropometric, and Beverage Intake Questionnaire (sugar-sweetened beverage) survey data. Setting The study took place at community clinics in Hawai’i on the island of O’ahu. Participants One hundred individuals were evaluated, age 14 to 34 years. Main Outcome Measures We used VCTE Fibroscan® with CAP scoring to identify the presence of hepatocyte steatosis (fatty liver). Results Overall MASLD prevalence in the sample was 44% (95% confidence interval: 34.1%-54.3%). In participants with MASLD, obese Native Hawaiian and other Pacific Islanders (62%) and nonobese Asians (43%) had the highest rates of MASLD. Conclusion This pilot evaluation of the AYA NHOPI and Asian MASLD population in Hawai’i shows a higher rate of MASLD than those reported in other parts of the United States. Larger population health studies are indicated to expand our knowledge of MASLD in the Hawaiian Islands.

Having diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited. To examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024. Cross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024. Participation in a clinical drug trial. Comparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion. In this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%). In this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.