Prevalence of low vitamin D levels among older US Asian and Pacific Islander adults.

While US Asian and Pacific Islander adults have lower 25-hydroxyvitamin D (25(OH)D) levels than White adults, ethnic subgroup data remain limited. In a large California population, the adjusted prevalence of 25(OH)D < 20 ng/mL (50 nmol/L) was 1.5- to 2.7-fold higher for Asian/Pacific Islander compared to White adults, with substantial variation by ethnicity. PURPOSE: US Asian and Pacific Islander (PI) adults generally have lower 25-hydroxyvitamin D [25(OH)D] levels than non-Hispanic White (NHW) adults, but subgroup data remain limited. We compared sex- and ethnicity-specific prevalence of low 25(OH)D among older Asian/PI and NHW adults. METHODS: Data from 102,556 Asian/PI and 381,724 NHW adults aged 50-89 years with measured 25(OH)D in 2012-2019 and body mass index (BMI, within ± 1 year) were examined in a California healthcare system. Low 25(OH)D < 20 ng/mL (50 nmol/L) was examined by race and ethnicity. Covariates included age, smoking, BMI, and season of measurement. Modified Poisson regression was used to estimate prevalence ratios (aPR), adjusting for covariates. RESULTS: Among 31,287 Asian/PI men and 71,269 Asian/PI women, the prevalence of low 25(OH)D was 22.6% and 14.7%, respectively, significantly higher than observed for 122,162 NHW men (12.3%) and 259,562 NHW women (9.9%). Within Asian/PI subgroups, low 25(OH)D prevalence ranged from 17 to 18% (Korean, Japanese, Filipino), 22 to 24% (Chinese, Vietnamese), 28% (South Asian), and 35% (Native Hawaiian/PI) among men and 11 to 14% (Japanese, Filipina, Chinese, Korean), 17 to 18% (South Asian, Vietnamese), and 26% (Native Hawaiian/PI) among women. The corresponding aPRs (NHW reference) for men and women were as follows: Native Hawaiian/PI, 2.70 and 2.34; South Asian, 2.56 and 2.07; Vietnamese, 2.17 and 2.31; Chinese, 2.04 and 1.89; Korean, 1.60 and 1.85; Filipino, 1.58 and 1.52; and Japanese, 1.58 and 1.49 (p < 0.001). CONCLUSION: In a large US healthcare population of older Asian/PI adults, low 25(OH)D prevalence was 1.5- to 2.7-fold higher for Asian/PI compared to NHW adults, with substantial variation by sex and ethnicity.

REST-dependent downregulation of von Hippel-Lindau tumor suppressor promotes autophagy in SHH-medulloblastoma.

The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella. In SHH medulloblastoma tumor xenografts, REST elevation is strongly correlated with increased expression of the hypoxia-inducible factor 1-alpha (HIF1α)-a positive regulator of autophagy, and with reduced expression of the von Hippel-Lindau (VHL) tumor suppressor protein - a component of an E3 ligase complex that ubiquitinates HIF1α. Human SHH-medulloblastoma tumors with higher REST expression exhibit nuclear localization of HIF1α, in contrast to its cytoplasmic localization in low-REST tumors. In vitro, REST knockdown promotes an increase in VHL levels and a decrease in cytoplasmic HIF1α protein levels, and autophagy flux. In contrast, REST elevation causes a decline in VHL levels, as well as its interaction with HIF1α, resulting in a reduction in HIF1α ubiquitination and an increase in autophagy flux. These data suggest that REST elevation promotes autophagy in SHH medulloblastoma cells by modulating HIF1α ubiquitination and stability in a VHL-dependent manner. Thus, our study is one of the first to connect VHL to REST-dependent control of autophagy in a subset of medulloblastomas.

Mapping the Single-Cell Differentiation Landscape of Osteosarcoma.

PURPOSE: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival. EXPERIMENTAL DESIGN: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas. RESULTS: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify each cell's lineage commitment. Projecting a bulk RNA-sequencing osteosarcoma dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes. CONCLUSIONS: Our study quantifies osteosarcoma differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.

Screening for Food and Nutrition Insecurity in the Healthcare Setting: A Cross-Sectional Survey of Non-Medicaid Insured Adults in an Integrated Healthcare Delivery System.

OBJECTIVES: Healthcare screening identifies factors that impact patient health and well-being. Hunger as a Vital Sign (HVS) is widely applied as a screening tool to assess food security. However, there are no common practice screening questions to identify patients who are nutrition insecure or acquire free food from community-based organizations. This study used self-reported survey data from a non-Medicaid insured adult population approximately one year after the start of the COVID-19 pandemic (2021). The survey examined the extent to which the HVS measure might have under-estimated population-level food insecurity and/or nutrition insecurity, as well as under-identified food and nutrition insecurity among patients being screened for social risks in the healthcare setting. METHODS: Data from a 2021 English-only mailed/online survey were analyzed for 2791 Kaiser Permanente Northern California (KPNC) non-Medicaid insured members ages 35-85 years. Sociodemographics, financial strain, food insecurity, acquiring free food from community-based organizations, and nutrition insecurity were assessed. Data from respondents' electronic health records were abstracted to identify adults with diet-related chronic health conditions. Data were weighted to the age × sex × racial/ethnic composition of the 2019 KPNC adult membership. Differences between groups were evaluated for statistical significance using adjusted prevalence ratios (aPRs) derived from modified log Poisson regression models. RESULTS: Overall, 8.5% of participants reported moderate or high food insecurity, 7.7% had acquired free food from community-based organizations, and 13% had nutrition insecurity. Black and Latino adults were significantly more likely than White adults to have food insecurity (17.4% and 13.1% vs 5.6%, aPRs = 2.97 and 2.19), acquired free food from community-based organizations (15.1% and 15.3% vs 4.1%, aPRs = 3.74 and 3.93), nutrition insecurity (22.1% and 23.9% vs 7.9%, aPRs = 2.65 and 2.64), and food and nutrition insecurity (32.4% and 32.5% vs 12.3%, aPRs = 2.54 and 2.44). Almost 20% of adults who had been diagnosed with diabetes, prediabetes, ischemic CAD, or heart failure were food insecure and 14% were nutrition insecure. CONCLUSIONS: Expanding food-related healthcare screening to identify and assess food insecurity, nutrition insecurity, and use of community-based emergency food resources together is essential for supporting referrals that will help patients achieve optimal health.

U.S. Filipino Adults Have Elevated Prevalence of Hypertension Across the Adult Lifespan: Findings From a Cross-Sectional Electronic Health Record Study.

Introduction: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults. Methods: This cross-sectional study used 2015-2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30-79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by race and ethnicity overall and by 10-year age decade from ages 30-39 years to 70-79 years. The prevalence of hypertension among 5 racial and ethnic groups was compared within each decade (with Filipino as the reference), adjusting for age, English language, diabetes, smoking, and weight category. Results: Decade-specific prevalence of hypertension among Filipino men and women, respectively, was 9.7% and 8.5% for ages 30-39 years, 26.0% and 23.9% for ages 40-49 years, 45.9% and 44.4% for ages 50-59 years, 65.4% and 63.9% for ages 60-69 years, and 82.1% and 82.9% for ages 70-79 years. Across all age decades, hypertension prevalence among Filipino adults largely tracked with Black adults and was much higher than among South Asian, Chinese, White, and Hispanic adults. This pattern remained after adjusting for covariates, with the largest differences observed for adults aged <60 years. Conclusions: Similar to Black adults, Filipino adults have persistently higher hypertension prevalence than South Asian, Chinese, Hispanic, and White adults across the adult lifespan. These findings underscore the importance of surveillance and prevention efforts for this high-risk Asian group beginning in early adulthood.

Cancer Patients' Preferences and Perceptions of Advantages and Disadvantages of Telehealth Visits During the COVID-19 Pandemic.

PURPOSE: We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters. METHODS: We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use. RESULTS: The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated (45% ≥bachelor's degree). For the first postdiagnosis discussion visit, 83% of patients preferred IP, followed by video (27%) and phone (18%). For follow-up visits, 52% of patients preferred IP, 50% video, and 37% phone. For discussions of bad news and sensitive topics, respectively, 68% and 62% preferred IP, 44% and 48% video, and 32% and 41% phone visits. Delivery of good news was acceptable through IP (49%), video (52%), or phone (49%) visits. Perceived advantages of IP visits were greater feelings of connection with their doctor (58%), confidence in physical examinations (73%), and ease in showing things (67%) and talking (51%) to the doctor. Advantages of telehealth visits included saved time (72%) and money (38%), less infection exposure (64%), less travel concerns (45%), and ability to include more people (28%). Of 24% of patients who felt video visits would be hard, 51% cited poor internet, 41% lack of an adequate device, and 28% difficulty signing on. CONCLUSION: Our results support continued use and reimbursement for telehealth visits with patients with cancer for most types of clinical encounters, including clinical trials.

Overview of CD70 as a Potential Therapeutic Target for Osteosarcoma.

Osteosarcoma is a primary malignant bone tumor. Effective chemotherapy regimens for refractory disease are scarce, accounting for no improvement in survival. Immune-based cell therapies have emerged as novel alternatives. However, advancements with these therapies have been seen mostly when immune cells are armed to target specific tumor Ags. Recent studies identified cluster of differentiation 70 (CD70) as a promising target to osteosarcoma particularly because CD70 is highly expressed in osteosarcoma lung metastases (Pahl et al. 2015. Cancer Cell Int. 15: 31), and its overexpression by tumors has been correlated with immune evasion and tumor proliferation (Yang et al. 2007. Blood 110: 2537-2544). However, the limited knowledge of the overall CD70 expression within normal tissues and the potential for off-target effect pose several challenges (Flieswasser et al. 2022. J. Exp. Clin. Cancer Res. 41: 12). Nonetheless, CD70-based clinical trials are currently ongoing and are preliminarily showing promising results for patients with osteosarcoma. The present review sheds light on the recent literature on CD70 as it relates to osteosarcoma and highlights the benefits and challenges of targeting this pathway.

Dissociation protocols used for sarcoma tissues bias the transcriptome observed in single-cell and single-nucleus RNA sequencing.

BACKGROUND: Single-cell RNA-seq has emerged as an innovative technology used to study complex tissues and characterize cell types, states, and lineages at a single-cell level. Classification of bulk tumors by their individual cellular constituents has also created new opportunities to generate single-cell atlases for many organs, cancers, and developmental models. Despite the tremendous promise of this technology, recent evidence studying epithelial tissues and diverse carcinomas suggests the methods used for tissue processing, cell disaggregation, and preservation can significantly bias gene expression and alter the observed cell types. To determine whether sarcomas - tumors of mesenchymal origin - are subject to the same technical artifacts, we profiled patient-derived tumor explants (PDXs) propagated from three aggressive subtypes: osteosarcoma (OS), Ewing sarcoma (ES), desmoplastic small round cell tumor (DSRCT). Given the rarity of these sarcoma subtypes, we explored whether single-nuclei RNA-seq from more widely available archival frozen specimens could accurately be identified by gene expression signatures linked to tissue phenotype or pathognomonic fusion proteins. RESULTS: We systematically assessed dissociation methods across different sarcoma subtypes. We compared gene expression from single-cell and single-nucleus RNA-sequencing of 125,831 whole-cells and nuclei from ES, DSRCT, and OS PDXs. We detected warm dissociation artifacts in single-cell samples and gene length bias in single-nucleus samples. Classic sarcoma gene signatures were observed regardless of the dissociation method. In addition, we showed that dissociation method biases could be computationally corrected. CONCLUSIONS: We highlighted transcriptional biases, including warm dissociation and gene-length biases, introduced by the dissociation method for various sarcoma subtypes. This work is the first to characterize how the dissociation methods used for sc/snRNA-seq may affect the interpretation of the molecular features in sarcoma PDXs.

Advance Directives for Patients With Breast Cancer: Applying the Right Info/Right Care/Right Patient/Right Time Oncology Model.

Background Advance directives (AD) are an important component of life care planning for patients undergoing treatment for cancer; however, there are few effective interventions to increase AD rates. In this quality improvement project, the authors integrated AD counseling into a novel right info/right care/right patient/right time (4R) sequence of care oncology delivery intervention for breast cancer patients in an integrated health care delivery system. Methods The authors studied two groups of patients with newly diagnosed breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at a single facility. The usual care (UC) cohort (N = 139) received care from October 1, 2019 to September 30, 2020. The 4R cohort (N = 141) received care from October 1, 2020 to September 30, 2121 that included discussing AD completion with a health educator prior to surgery. The authors used bivariate analyses to assess whether the AD intervention increased AD completion rates and to identify factors influencing AD completion. Results The UC and 4R cohorts were similar in age, gender, race/ethnicity, interpreter need, Elixhauser comorbidity index, National Comprehensive Cancer Network distress score ≥ 5, surgery type, stage, histology, grade, and Estrogen receptor/Progesterone receptor/ human epidermal growth factor receptor 2 (ER/PR/HER2) status. AD completion rates prior to surgery were significantly higher for the 4R vs UC cohort (73.8%, 95% confidence interval [CI] [66.5%-81.0%] vs 15.1%, 95% CI [9.2%-21.1%], p < .01) and did not significantly differ by age, race, need for interpreter, or distress scores. Conclusion Incorporation of a health educator discussion into a 4R care sequence plan significantly increased rates of time-sensitive AD completion.

Trends in Smoking-Specific Lung Cancer Incidence Rates Within a US Integrated Health System, 2007-2018.

BACKGROUND: At least 10% of lung cancers arise in adults who have never used tobacco. Data remain inconclusive on whether lung cancer incidence has been increasing among adults who have never used tobacco. RESEARCH QUESTION: How have age-adjusted incidence rates of lung cancer changed temporally, especially among adults who have never used tobacco? STUDY DESIGN AND METHODS: Trends in lung cancer incidence were examined using linked electronic health record and cancer registry data on a dynamic cohort of adults ≥ 30 years of age at risk of incident lung cancer between January 1, 2007, and December 31, 2018, from an integrated health-care system in northern California. Truncated age-adjusted lung cancer incidence rates and average annual percentage change (AAPC) in rates were estimated, overall and separately for adults who have ever and never used tobacco by age, sex, and race or ethnicity. RESULTS: The cohort included 3,751,348 adults (52.5% female, 48.0% non-Hispanic White, 63.1% have never used tobacco), among whom 18,627 (52.7% female, 68.6% non-Hispanic White, 15.4% have never used tobacco) received a diagnosis of lung cancer. The overall lung cancer incidence rate declined from 91.1 to 63.7 per 100,000 person-years between 2007 and 2009 and between 2016 and 2018 (AAPC, -3.9%; 95% CI, -4.2% to -3.6%). Among adults who have ever used tobacco, incidence rates declined overall from 167.0 to 113.4 per 100,000 person-years (AAPC, -4.2%; 95% CI, -4.4% to -3.9%) and, to varying degrees, within all age, sex, and racial or ethnic groups. Among adults who have never used tobacco, incidence rates were relatively constant, with 3-year-period estimates ranging from 19.9 to 22.6 per 100,000 person-years (AAPC, 0.9%; 95% CI, -0.3% to 2.1%). Incidence rates for adults who have never used tobacco seemed stable over time, within age, sex, and racial or ethnic groups, except for those of Asian and Pacific Islander (API) origin (AAPC, 2.0%; 95% CI, 0.1%-3.9%), whose rates were about twice as high compared with their counterparts. INTERPRETATION: These observed trends underscore the need to elucidate further the cause of lung cancer in adults who have never used tobacco, including why incidence is higher and rising in API adults who have never used tobacco.

Cardiovascular Disease Risk Factors Among Middle-Aged and Older Adult Vietnamese American Members of a Northern California Health Plan.

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan. METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m2), obesity (body mass index ≥27.5 kg/m2), prediabetes, diabetes, and hypertension among middle-aged (n = 12 757; aged 45-64 years) and older (n = 3418; aged 65-84 years) Vietnamese adults, including 37.8% whose preferred language was Vietnamese. Findings were compared with East Asian adults. RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and <1% for women in both age groups. Obesity prevalence was 12.0% for older men, 17.9% for middle-aged men, and 10% for women in both age groups. Among middle-aged men and women, 20.9% and 17.0% had hypertension and 13.5% and 8.5% had diabetes, respectively. Among older men and women, 64.0% and 60.0% had hypertension and 32.8% and 29.3% had diabetes, respectively. In both age groups, Vietnamese language preference was associated with higher risk of smoking (men only) and of diabetes and hypertension (women only). Compared with East Asian adults, Vietnamese adults had lower obesity prevalence but similar prevalence of diabetes, prediabetes, and hypertension. Vietnamese men were more likely and Vietnamese women less likely than East Asian adults to be current smokers. CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.

Fostering a High-Functioning Team in Cancer Care Using the 4R Oncology Model: Assessment in a Large Health System and a Blueprint for Other Institutions.

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system. METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. RESULTS: We formed an internally and externally recognized team of 24 specialties committed to a shared goal of delivering multidisciplinary care at the optimal time and sequence from a patient-centric viewpoint. The team conducted 40 optimizations of interdependent care (22 for breast, seven for lung, and 11 for both cancers) at four points in the care continuum and established an ongoing teamwork adaptation process. Half of the optimizations entailed low effort, while 30% required high level of effort; 78% resulted in improved process efficiency. CONCLUSION: 4R facilitated development of a large high-functioning team and enabled 40 optimizations of interdependent care along the cancer care continuum in a feasible way. 4R may be an effective approach for fostering high-functioning teams, which could contribute to improving viability of the oncology workforce. Our intervention and taxonomy of results serve as a blueprint for other institutions motivated to strengthen teamwork to improve patient-centered care.

Differences in Health Characteristics of Geographic Subgroups of Arab Americans in a Northern California Health Plan.

INTRODUCTION: Arab Americans are a diverse ethnic group originating from a large geographic area in the Middle East and North Africa (MENA). We aim to characterize differences in health between Arab Americans from different geographic subgroups within MENA. METHODS: We used cross-sectional electronic health record (EHR) data for a subset of 4913 Arab Americans aged 20-84 in a 2016 Northern California health plan study cohort who could be assigned to one of 4 geographic subgroups (Gulf, African, Levant, and Other) based on EHR ethnicity data. We calculated age-adjusted prevalence estimates for men and women and used generalized linear models to compare Gulf, African, and Other subgroups to Levant Arabs on risk factors (obesity and smoking), chronic conditions (diabetes, hypertension, hyperlipidemia, and asthma), and mental health (depression and anxiety). RESULTS: Among women, prevalence of smoking was lower among Gulf, African, and Other Arabs than Levant Arabs. Among men, prevalence of obesity, diabetes, and hyperlipidemia was lower among Gulf, African, and Other Arabs than Levant Arabs, while prevalence of depression was higher for these subgroups than Levant Arabs. DISCUSSION: We found substantial differences in health characteristics across Arab Americans from different geographic subgroups. Our results suggest that more detailed race and ethnicity information should be collected on Arab Americans to better understand their diverse health risks.

Prognostic Value of Cell-Surface Vimentin-Positive CTCs in Pediatric Sarcomas.

BACKGROUND: Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety. METHODS: Here, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease. RESULTS: We constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests. CONCLUSIONS: Our findings indicate that CSV+ CTCs have prognostic value and can possibly serve as a measure of disease burden.

Understanding differences within ethnic group designation: comparing risk factors and health indicators between Iranian and Arab Americans in Northern California.

BACKGROUND: The Middle Eastern and North African (MENA) ethnic group is a diverse group composed of two primary subsets in the United States: Iranian and Arab Americans. We aimed to compare health risk factors, chronic health conditions, and mental health conditions of Iranian and Arab American adults in Northern California. METHODS: We used cross-sectional electronic health record (EHR) data from a 2016 Northern California health plan study cohort to compare adults classified as Iranian or Arab American based on ethnicity, language, or surname. We produced age-standardized prevalence estimates of obesity, smoking, hyperlipidemia, prediabetes, diabetes, hypertension, depression, and anxiety for Iranian and Arab American men and women by age group (35-44, 45-64, and 65-84) and overall (35-84). We used generalized linear models to calculate prevalence ratios (PR) to compare Iranian and Arab American adults ages 35-84 on all health indicators. RESULTS: Compared to Arab Americans, Iranian Americans had a lower prevalence of obesity (PR: 0.77, 95% confidence interval, CI: 0.73, 0.82), current smoking (PR: 0.80, 95% CI: 0.73, 0.89), and ever smoking (PR: 0.95, 95% CI: 0.91, 0.99), but a higher prevalence of hyperlipidemia (PR: 1.09, 95% CI: 1.06, 1.12), prediabetes (PR: 1.12, 95% CI: 1.09, 1.16), depression (PR; 1.41, 95% CI: 1.30, 1.52), and anxiety (PR: 1.52, 95% CI: 1.42, 1.63). Similar patterns were observed for men and women. CONCLUSION: This work supports the need to collect granular data on race and ethnicity within the MENA ethnic group to improve identification in clinical care settings and population health reporting to better address the physical and mental health needs of different MENA subgroups.

Racial/ethnic, gender, and age group differences in cardiometabolic risks among adults in a Northern California health plan: a cross-sectional study.

BACKGROUND: In the U.S., the prevalence of diabetes and hypertension are higher among African American/Black (Black), Latinx, and Filipino adults than non-Hispanic White (White) and Chinese adults. We compared the racial/ethnic-specific prevalence of several modifiable cardiometabolic risks in an insured adult population to identify behaviors that may drive racial/ethnic differences in cardiometabolic health. METHODS: This cross-sectional study used data for middle-aged (35-64) and older (65-79) Kaiser Permanente Northern California (KPNC) adult health plan members. Smoking status and BMI were derived from electronic health record data. Weighted pooled self-reported data from the 2014/2015 and 2017 KPNC Member Health Survey cycles were used to estimate daily number of servings of fruits/vegetables, general sodium avoidance, sugar-sweetened beverage (SSB) consumption frequency, alcohol use within daily recommended limit, weekly exercise frequency, and number of hours of sleep daily. Age-standardized estimates of all cardiometabolic risks were produced for middle-aged and older-aged women and men in the five racial/ethnic groups. Analyses focused on racial/ethnic differences within age-gender groups and gender and age group differences within racial/ethnic groups. RESULTS: In both age groups, Black, Latinx, and Filipino adults were more likely than White and Chinese adults to have overweight and obesity and were less likely to engage in health promoting dietary (fruit/vegetable and SSB consumption, sodium avoidance (women only)) and sleep behaviors. Middle-aged Black and Filipino men were more likely than White men to be current smokers. Less racial/ethnic variation was seen in exercise frequency. Significant gender differences were observed for dietary behaviors overall and within racial/ethnic groups, especially among middle-aged adults; however, these gender differences were smaller for sleep and exercise. Age differences within gender and racial/ethnic groups were less consistent. Racial/ethnic and gender differences in these behaviors were also seen in the subsample of adults with diabetes and/or hypertension and in the subsample of adults who reported they were trying to engage in health promoting behaviors. CONCLUSIONS: Black, Latinx, and Filipino adults were more likely than White and Chinese adults to report dietary and sleep behaviors associated with development and worsening of cardiometabolic conditions, with men exhibiting poorer dietary behaviors than women.

Health Risks and Chronic Health Conditions among Arab American and White Adults in Northern California.

Objectives: To characterize the prevalence of chronic cardiovascular conditions and risk factors among Arab American adults stratified by sex and compare these with non-Hispanic Whites. Design: Cross-sectional study using electronic health record data from visits between January 2015 and December 2016. Age-adjusted prevalence estimates were calculated for men and women and compared using generalized linear models. Setting: Kaiser Permanente health plan in Northern California. Participants: Non-Hispanic White (N=969,566) and Arab American (N=18,072) adult members. Main Outcome Measures: Sex-stratified prevalence and prevalence ratios of diabetes, pre-diabetes, hypertension, and hyperlipidemia diagnosed by December 2016 and of obesity, ever smoking, and current smoking status. Results: Arab American men had a significantly higher prevalence of ever smoking (41.8 vs 40.8%), diabetes (17.3 vs 12.5%), and hyperlipidemia (40.8 vs 34.7%) than White men, but a significantly lower prevalence of obesity (34.4 vs 37.8%) and hypertension (30.5 vs 33.3%). Arab American women had a significantly higher prevalence of diabetes (11.1 vs 8.7%) and hyperlipidemia (31.5 vs 28.3%) than White women but significantly lower prevalence of obesity (31.0 vs 34.2%), ever smoking (24.8 vs 34.5%), and hypertension (25.8 vs 28.4%). Conclusions: Hospital and health systems should intentionally collect data on Middle Eastern and North African ethnicity in electronic health records to identify and reduce the disparities this minority group faces.

Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Autophagy in Osteosarcoma.

Osteosarcoma (OS) remains a difficult disease to treat. The standard chemotherapy regimen has not improved survival for the past three decades. Resistance to chemotherapy remains a challenge and constitutes a major concern to clinical investigators. Autophagy has been recognized as a survival mechanism implicated in resistance to chemotherapy. We previously demonstrated chemotherapy to induce autophagy in OS. However, whether induction of autophagy will lead to survival or death has been the focus of many laboratories. Autophagy is a very context-dependent process, and no specific biomarker has been identified to define whether the process will lead to survival or death. In the present chapter, we present some of the mechanisms involved in the process of autophagy and summarize some of the most recent work related to autophagy in OS and the challenges encountered with the use of old and new autophagy inhibitors.