HIV Associated Lung Cancer: Unique Clinicopathologic Features and Immune Biomarkers Impacting Lung Cancer Screening and Management.

OBJECTIVES: Lung cancer contributes significantly to morbidity and mortality in people with HIV (PWH). We study the clinicopathologic characteristics and immune microenvironment in HIV associated lung cancer. MATERIAL AND METHODS: Clinicopathological characteristics including immunotherapy outcomes were collected for 174 PWH diagnosed with lung cancer. Immunohistochemical staining for PD-L1, CD4, and CD8 was performed. RESULTS: At diagnosis, patients with HIV associated lung cancer were significantly younger (56.9 vs. 69 years, P < .0001) and more frequently had advanced disease (70% vs. 53%, P = .01). The majority were African American (60% vs. 42%, P < .0001) and were smoking at the time of diagnosis or smoked in the past (98% vs. 86%, P = .0001). Only 10% of HIV associated lung cancer was diagnosed through the screening program. The median CD4+ lymphocyte count was 334 cells/µL, 31% had a CD4 ≤200 cells/µL and 63% of the cohort was virally suppressed. HIV associated non-small-cell lung cancer(NSCLC) was characterized by limited PD-L1 expression compared to the HIV negative cohort, 64% vs. 31% had TPS <1%, and 20% vs. 34% had TPS≥50%, respectively (P = .04). Higher CD8+ TILs were detected in PD-L1-high tumors (P < .0001). 50% of patients achieved disease control in the metastatic setting with the use of immunotherapy, and there were no new safety signals in 19 PWH treated with immunotherapy. CONCLUSION: Lung cancer in PWH demonstrates unique features highlighting the need for a specialized screening program. Despite low PD-L1 expression, immunotherapy is well tolerated with reasonable disease control. Altered immune system in lung cancer pathogenesis in PWH should be further investigated.

Waist-to-height ratio associated cardiometabolic risk phenotype in children with overweight/obesity.

BACKGROUND: Childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study. METHODS: Baseline data from 360 children (7-12 years, mean Body Mass Index (BMI) ≥ 85th percentile for age and sex) were used to calculate WHtR tertiles by sex, male: ≤ 0.55 (T1), > 0.55- ≤ 0.59 (T2), > 0.59 (T3); female: ≤ 0.56 (T1), > 0.56- ≤ 0.6 (T2), > 0.6 (T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR < 2.6). Liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were categorized as normal vs. elevated (AST of < 36.0 µkat/L or ≥ 36.0 µkat/L; ALT of < 30.0 µkat/L or ≥ 30.0 µkat/L; ALT > 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes. RESULTS: Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34-14.52] and T2 [OR, 95%CI: 4.81, 1.94-11.92] and females in T3 [OR, 95%CI: 5.06, 2.10-12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01-8.41] fold higher among females in T3 compared to T1. CONCLUSION: In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome.

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria.

BACKGROUND AND OBJECTIVES: Lupus nephritis remains a common cause of morbidity and mortality in systemic lupus erythematosus (SLE). Current guidelines recommend performing a kidney biopsy at a urine protein-creatinine ratio of ≥0.5 g/g. However, cross-sectional studies reported a high prevalence of active histologic lupus nephritis lesions, and even chronic irreversible scarring, in patients with low-grade proteinuria. This study was initiated to assess disease progression in patients with SLE and low-grade proteinuria to identify risk factors for progression to overt proteinuria suggestive of clinical lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with SLE who had an incident urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g without known lupus nephritis were identified from the Einstein Rheumatic Disease Registry. Patients who developed a random urinary protein-creatinine ratio of ≥0.5 g/g with or without biopsy during the follow-up period were defined as "progressors." Patients who progressed to a urinary protein-creatinine ratio of ≥0.5 g/g within 2 years of developing a urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g were defined as "fast progressors," a subgroup expected to benefit most from early biopsies and therapeutic interventions. RESULTS: Among 151 eligible patients with SLE and low-grade proteinuria at study entry, 76 (50%) progressed to a urinary protein-creatinine ratio of ≥0.5 g/g, of which 44 underwent a clinically indicated biopsy. The median (interquartile range) time from a urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g to progression was 1.2 (0.3-3.0) years. Of the 20 biopsies performed in the first 2 years, 16 specimens showed active, treatable lupus nephritis. Low complement and shorter SLE duration at low-grade proteinuria onset were associated with progression to overt proteinuria across different analyses. Other associated factors included hypertension, diabetes mellitus, younger age, and the presence of hematuria. CONCLUSIONS: In this longitudinal cohort of patients with SLE and low-grade proteinuria at study entry, over half progressed to a urinary protein-creatinine ratio of ≥0.5 g/g in a short time period.

ASSOCIATION OF SOCIAL NEEDS WITH UNCONTROLLED VIREMIA IN PEOPLE WITH HIV.

Using a tool integrated into the electronic health record, we determined prevalence of 10 social needs among 377 people with HIV (PWH) and 27,833 patients without HIV receiving care in the Montefiore Health System. PWH (median age 53) were 55% women, 41% Black, 44% Hispanic. 33% of PWH reported at least one social need vs. 18% among patients without HIV, with healthcare transportation and housing needs significantly higher among PWH in adjusted analyses. PWH reporting transportation needs were 27% less likely to be virologically suppressed (< 200 copies/mL, adjusted prevalence ratio 0.73, 95% CI 0.55-0.96) compared with PWH without transportation needs.

RESUMEN: Por medio del uso de encuestas integradas en el registro electrónico de salud, determinamos la prevalencia de 10 necesidades sociales entre 377 personas con VIH (PCV) y 27 833 pacientes sin VIH que reciben atención en el Montefiore Health System. PCV (edad mediana de 53 años) fueron 55% mujeres, 41% negras, 44% hispanas. 33% de PCV reportó al menos una necesidad social vs. 18% de los pacientes sin VIH, siendo las necesidades de transporte a cuidados de salud y de vivienda significativamente mayores en PCV en análisis multivariable ajustado. PCV con necesidades de transportación fueron 27% menos probables de tener supresión viral (< 200 copias/ml, razón de prevalencias ajustada 0.73, IC 95% 0.55­0.96) comparada con PCV sin necesidades de transportación.

Spillover Effects of a Family-Based Childhood Weight-Management Intervention on Parental Nutrient Biomarkers and Cardiometabolic Risk Factors.

BACKGROUND: Parental involvement has been shown to favorably affect childhood weight-management interventions, but whether these interventions influence parental diet and cardiometabolic health outcomes is unclear. OBJECTIVES: The aim was to evaluate whether a 1-y family-based childhood weight-management intervention altered parental nutrient biomarker concentrations and cardiometabolic risk factors (CMRFs). METHODS: Secondary analysis from a randomized-controlled, parallel-arm clinical trial (NCT00851201). Families were recruited from a largely Hispanic population and assigned to either standard care (SC; American Academy of Pediatrics overweight/obesity recommendations) or SC + enhanced program (SC+EP; targeted diet/physical activity strategies, skill building, and monthly support sessions). Nutrient biomarkers (plasma carotenoids and fat-soluble vitamins, RBC fatty acid profiles) and CMRFs (BMI, blood pressure, glucose, insulin, lipid profile, inflammatory and endothelial dysfunction markers, adipokines) were measured in archived samples collected from parents of participating children at baseline and end of the 1-y intervention. RESULTS: Parents in both groups (SC = 106 and SC+EP = 99) had significant reductions in trans fatty acid (-14%) and increases in MUFA (2%), PUFA n-6 (É·-6) (2%), PUFA n-3 (7%), and ß-carotene (20%) concentrations, indicative of lower partially hydrogenated fat and higher vegetable oil, fish, and fruit/vegetable intake, respectively. Significant reductions in high-sensitivity C-reactive protein (hsCRP; -21%) TNF-α (-19%), IL-6 (-19%), and triglycerides (-6%) were also observed in both groups. An additional significant improvement in serum insulin concentrations (-6%) was observed in the SC+EP parents. However, no major reductions in BMI or blood pressure and significant unfavorable trajectories in LDL-cholesterol and endothelial dysfunction markers [P-selectin, soluble intercellular adhesion molecule (sICAM), thrombomodulin] were observed. Higher carotenoid, MUFA, and PUFA (n-6 and n-3) and lower SFA and trans fatty acid concentrations were associated with improvements in circulating glucose and lipid measures, inflammatory markers, and adipokines. CONCLUSIONS: The benefits of a family-based childhood weight-management intervention can spill over to parents, resulting in apparent healthier dietary shifts that are associated with modest improvements in some CMRFs.

Molecular markers of risk of subsequent invasive breast cancer in women with ductal carcinoma in situ: protocol for a population-based cohort study.

INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of invasive breast cancer (IBC). Many DCIS patients are either undertreated or overtreated. The overarching goal of the study described here is to facilitate detection of patients with DCIS at risk of IBC development. Here, we propose to use risk factor data and formalin-fixed paraffin-embedded (FFPE) DCIS tissue from a large, ethnically diverse, population-based cohort of 8175 women with a first diagnosis of DCIS and followed for subsequent IBC to: identify/validate miRNA expression changes in DCIS tissue associated with risk of subsequent IBC; evaluate ipsilateral IBC risk in association with two previously identified marker sets (triple immunopositivity for p16, COX-2, Ki67; Oncotype DX Breast DCIS score); examine the association of risk factor data with IBC risk. METHODS AND ANALYSIS: We are conducting a series of case-control studies nested within the cohort. Cases are women with DCIS who developed subsequent IBC; controls (2/case) are matched to cases on calendar year of and age at DCIS diagnosis. We project 485 cases/970 controls in the aim focused on risk factors. We estimate obtaining FFPE tissue for 320 cases/640 controls for the aim focused on miRNAs; of these, 173 cases/346 controls will be included in the aim focused on p16, COX-2 and Ki67 immunopositivity, and of the latter, 156 case-control pairs will be included in the aim focused on the Oncotype DX Breast DCIS score®. Multivariate conditional logistic regression will be used for statistical analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Boards of Albert Einstein College of Medicine (IRB 2014-3611), Kaiser Permanente Colorado, Kaiser Permanente Hawaii, Henry Ford Health System, Mayo Clinic, Marshfield Clinic Research Institute and Hackensack Meridian Health, and from Lifespan Research Protection Office. The study results will be presented at meetings and published in peer-reviewed journals.

Brief Report: Acute Kidney Injury in People Living With HIV Hospitalized With Coronavirus Disease 2019: Clinical Characteristics and Outcomes.

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.

Risk factors for breast cancer development by tumor characteristics among women with benign breast disease.

BACKGROUND: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown. METHODS: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models. RESULTS: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size. CONCLUSION: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

Clinical Outcomes and Inflammatory Markers by HIV Serostatus and Viral Suppression in a Large Cohort of Patients Hospitalized With COVID-19.

BACKGROUND: Limited data exist about clinical outcomes and levels of inflammatory and immune markers among people hospitalized with COVID-19 by HIV serostatus and by HIV viral suppression. SETTING: Large tertiary care health system in the Bronx, NY, USA. METHODS: We conducted a retrospective cohort study of 4613 SARS-CoV-2 PCR-positive patients admitted between March 10, 2020, and May 11, 2020. We examined in-hospital intubation, acute kidney injury (AKI), hospitalization length, and in-hospital mortality by HIV serostatus, and by HIV-viral suppression and CD4 counts among people living with HIV (PLWH) using adjusted competing risks regression. We also compared immune and inflammatory marker levels by HIV serostatus and viral suppression. RESULTS: Most patients were either non-Hispanic Black (36%) or Hispanic (37%); 100/4613 (2.2%) were PLWH, among whom 15 had detectable HIV viral load. PLWH compared to patients without HIV had increased intubation rates (adjusted hazard ratio 1.73 [95% CI: 1.12 to 2.67], P = 0.01). Both groups had similar rates of AKI, length of hospitalization, and death. No (0%) virally unsuppressed PLWH were intubated or died, versus 21/81 (26%, P = 0.04) and 22/81 (27%, P = 0.02) of virally suppressed PLWH, respectively. Among PLWH, higher CD4 T-cell counts were associated with increased intubation rates. C-reactive protein, IL-6, neutrophil counts, and ferritin levels were similar between virally suppressed PLWH and patients without HIV, but significantly lower for unsuppressed PLWH (all P < 0.05). CONCLUSIONS: PLWH had increased risk of intubation but similarly frequent rates of AKI and in-hospital death as those without HIV. Findings of no intubations or deaths among PLWH with unsuppressed HIV viral load warrant further investigation.

Infiltrating immune cells in benign breast disease and risk of subsequent invasive breast cancer.

BACKGROUND: It is well established that tumors are antigenic and can induce an immune response by the host, entailing lymphocytic infiltration of the tumor and surrounding stroma. The extent and composition of the immune response to the tumor, assessed through evaluation of tumor-infiltrating lymphocyte counts, has been shown in many studies to have prognostic and predictive value for invasive breast cancer, but currently, there is little evidence regarding the association between infiltrating immune cell counts (IICCs) in women with benign breast disease (BBD) and risk of subsequent invasive breast cancer. METHODS: Using a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest, we conducted a nested case-control study in which cases were women who developed a subsequent invasive breast cancer during follow-up and controls were individually matched to cases on age at BBD diagnosis. We assessed IICCs in normal tissue and in the BBD lesions, and we used unconditional logistic regression to estimate the multivariable odds ratios (OR) and 95% confidence intervals (CI) for the associations between IICCs and breast cancer risk. RESULTS: There was no association between the IICC in normal tissue (multivariable OR per 5% increase in IICC = 1.05, 95% CI = 0.96-1.16) or in the BBD lesion (OR per 5% increase in IICC = 1.06, 95% CI = 0.96-1.18) and risk of subsequent invasive breast cancer. Also, there were no associations within subgroups defined by menopausal status, BBD histology, BMI, and history of smoking. CONCLUSION: The results of this study suggest that IICCs in BBD tissue are not associated with altered risk of subsequent invasive breast cancer.

Algorithm to identify transgender and gender nonbinary individuals among people living with HIV performs differently by age and ethnicity.

PURPOSE: HIV research among transgender and gender nonbinary (TGNB) people is limited by lack of gender identity data collection. We designed an EHR-based algorithm to identify TGNB people among people living with HIV (PLWH) when gender identity was not systematically collected. METHODS: We applied EHR-based search criteria to all PLWH receiving care at a large urban health system between 1997 and 2017, then confirmed gender identity by chart review. We compared patient characteristics by gender identity and screening criteria, then calculated positive predictive values for each criterion. RESULTS: Among 18,086 PLWH, 213 (1.2%) met criteria as potential TGNB patients and 178/213 were confirmed. Positive predictive values were highest for free-text keywords (91.7%) and diagnosis codes (77.4%). Confirmed TGNB patients were younger (median 32.5 vs. 42.5 years, P < .001) and less likely to be Hispanic (37.1% vs. 62.9%, P = .03) than unconfirmed patients. Among confirmed patients, 15% met criteria only for prospective gender identity data collection and were significantly older. CONCLUSION: EHR-based criteria can identify TGNB PLWH, but success may differ by ethnicity and age. Retrospective versus intentional, prospective gender identity data collection may capture different patients. To reduce misclassification in epidemiologic studies, gender identity data collection should address these potential differences and be systematic and prospective.

Effect of a Family-Based Intervention on Nutrient Biomarkers, Desaturase Enzyme Activities, and Cardiometabolic Risk Factors in Children with Overweight and Obesity.

BACKGROUND: Developing dietary strategies to prevent excess weight gain during childhood is critical to stem the current obesity epidemic and associated adverse cardiometabolic consequences. OBJECTIVES: We aimed to assess how participation in a family-based weight-management intervention affected nutrient biomarkers and cardiometabolic risk factors (CMRFs) in children (7-12 y old; n = 321) with baseline BMI z score (BMIz) ≥85th percentile. METHODS: This was a secondary analysis from a randomized-controlled, parallel-arm clinical trial. Families of children, recruited from a largely Hispanic population, were assigned to Standard Care (SC; American Academy of Pediatrics overweight/obesity recommendations), or SC + Enhanced Program (SC + EP; 8 skill-building cores, monthly support sessions, targeted diet/physical activity strategies). Nutrient biomarkers (plasma carotenoids, fat-soluble vitamins, RBC fatty acid profiles, desaturase indexes) and CMRFs were measured in archived blood samples collected at baseline and the end of the 1-y intervention. RESULTS: Children in both groups had significantly lower trans fatty acid and higher pentadecylic acid (15:0), PUFA n-3, and ß-carotene concentrations, indicative of decreased hydrogenated fat and increased dairy, vegetable oil, fish, and fruit/vegetable intake, respectively. Similar changes were seen in de novo lipogenesis and desaturase indexes, as well as CMRFs (BMIz, lipid profile, inflammation, adipokines, liver enzymes) in both groups. Using multiple logistic regression, increase in carotenoids and decrease in endogenously synthesized SFA, MUFA, PUFA n-6, and desaturase indexes were associated with improvements in BMIz, blood pressure, lipid profile, glucose metabolism, inflammatory biomarkers, adipokines, and liver enzymes. Trans fatty acids were associated with improvements in BMIz, glucose metabolism, and leptin, with less favorable effects on inflammatory markers and adiponectin. CONCLUSIONS: Providing targeted family-based behavioral counseling, as part of SC, can help overweight/obese children adopt healthier eating patterns that are associated with modest improvements in BMIz and several CMRFs. Limited additional benefit was observed with SC + EP. These results provide critical data to design subsequent interventions to increase the impact of family-based obesity prevention programs.This trial was registered at clinicaltrials.gov as NCT00851201.

Hispanics/Latinos in the Bronx Have Improved Survival in Non-Small Cell Lung Cancer Compared with Non-Hispanic Whites.

BACKGROUND: Hispanics/Latinos are a growing yet understudied population in the United States (US). Despite lower socioeconomic status, Hispanics/Latinos tend to have similar or better health outcomes than Non-Hispanic Whites (NHWs). This phenomenon has not been conclusively studied for lung cancer. METHODS: Using a cohort of patients at Montefiore Medical Center (MMC) in the Bronx, NY, we examined factors related to lung cancer survival by race/ethnicity with an emphasis on Hispanics/Latinos. Subjects were diagnosed with non-small cell lung cancer (NSCLC) between 2004 and 2017. Demographic and clinical data were obtained from MMC's clinical systems and tumor-related information from MMC/Einstein's Cancer Registry. Survival was assessed using Cox proportional hazards modeling adjusted for clinical and sociodemographic factors including smoking. Factors related to survival within each major racial/ethnic group were examined. RESULTS: Hispanics/Latinos experienced decreased risk of death relative to NHWs [hazard ratio (HR) = 0.70, 95% confidence interval (95%CI) 0.57-0.86] overall and by sex (males: HR = 0.78, 95%CI 0.59-1.03, females: HR = 0.61, 95%CI 0.44-0.86). Decreased risk among Hispanics/Latinos relative to NHWs was evident in never-smokers (HR = 0.55, 95%CI 0.29-1.01), ever-smokers (HR = 0.72, 95%CI 0.57-0.90), younger subjects (HR = 0.73, 95%CI 0.54-0.99), and older subjects (HR = 0.72, 95%CI 0.53-0.97). Surgery was associated with improved survival in Hispanics/Latinos (HR = 0.60, 95%CI 0.43-0.85), and smoking with worse survival (HR = 1.56, 95%CI 1.02-2.39). Survival did not differ between Non-Hispanic Blacks and NHWs. CONCLUSIONS: In a poor urban community, Hispanics/Latinos experience improved survival from NSCLC compared to NHWs, which is not entirely explained by smoking. Future research should investigate the drivers of this benefit and differences in survival by Hispanic/Latino origin.

Triggers of Lapse and Relapse of Diet and Exercise in Behavioral Weight Loss.

OBJECTIVE: This study aimed to (1) develop instruments to evaluate situations that lead to lapse and relapse in diet and exercise and (2) prospectively investigate when and which psychosocial situations predict failure to lose weight in a clinical trial of intentional weight loss. METHODS: Participants were 469 individuals with overweight or obesity participating in a behavioral weight loss program (age: mean = 53.6 years, SD = 11.4; BMI: mean = 35.7 kg/m2 , SD = 6.5). RESULTS: The Cronbach alphas for the Diet Lapse and Relapse Triggers Scale and the Exercise Lapse and Relapse Triggers Scale were 0.93 and 0.91, respectively. Subscale alphas ranged from 0.60 to 0.96. Lapse and relapse were assessed at 3 and 9 months for associations with weight loss at 12 months. At 9 months, diet triggers were negative emotional states (beta = 0.11, P = 0.02) and urges (beta = 0.14, P = 0.01). Predicted social situations showed the opposite (beta = -0.09, P = 0.02). Exercise subscales were all nonsignificant. CONCLUSIONS: Findings suggest the ongoing importance of addressing negative emotional states and the contributing influence of urges. The novel finding that participants whose difficulties arise in social situations may do better over time requires further study.

Home Environment Factors and Health Behaviors of Low-income, Overweight, and Obese Youth.

Objectives: Home environment may influence children's health behaviors associated with obesity. In this study, we examined home environment factors associated with diet and physical activity behaviors of overweight or obese youth. Methods: We analyzed baseline data from child and parent/caregiver dyads enrolled in an urban family weight management program. Multivariable logistic regression examined how home environment (parenting practices, family meal habits, and home availability of fruits/vegetables, sugar-sweetened beverages (SSBs), screen media, and physical activity resources) are related to children's intake of fruit, vegetables, and SSBs, and moderate-vigorous physical activity and sedentary time (ST) after adjusting for potential confounders. Results: Children were more likely to consume fruit if their families frequently ate meals together and infrequently watched TV during meals, and more likely to consume vegetables with high fruit/vegetable availability and low SSB availability. Children were more likely to engage in ST if parents practiced monitoring and frequently watched TV during meals. Conclusions: Overweight or obese children appear to have healthier habits if their families eat meals together without watching TV and if healthy food choices are available in the home. Encouraging parents to focus these practices may promote healthier body weight in children.

A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis.

Dysregulation of miRNA expression may influence breast cancer progression, and experimental evidence suggests that miRNA silencing might suppress breast cancer metastasis. However, the relationship between miRNA and metastasis must be confirmed before this approach can be applied in the clinic. To this end, we conducted a two-stage study in a cohort of 3,760 patients with breast cancer to first identify and then validate the association between miRNA expression and risk of distant metastasis. The first stage (discovery) entailed miRNA sequencing of 126 case-control pairs; qPCR was used to validate the findings in a separate set of 80 case-control pairs. The 13 miRNAs most differentially expressed between cases and controls were combined into an miRNA score that was significantly associated with risk of distant metastasis in a logistic regression model that also included clinical variables (tumor size and number of positive lymph nodes) (ORper unit increase in score = 1.30; 95% confidence interval, 1.03-1.66). The results of this study suggest that in women with invasive breast cancer, a miRNA score that incorporates both clinical variables and miRNA expression levels in breast tumor tissue is moderately predictive of risk of subsequent distant metastasis. SIGNIFICANCE: A novel predictive scoring system for patients with breast cancer includes clinical variables and the expression levels of 13 miRNAs and may help to identify those at increased risk of distant metastasis.

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer.

BACKGROUND: Insights into the molecular pathogenesis of breast cancer might come from molecular analysis of tissue from early stages of the disease. METHODS: We conducted a case-control study nested in a cohort of women who had biopsy-confirmed benign breast disease (BBD) diagnosed between 1971 and 2006 at Kaiser Permanente Northwest and who were followed to mid-2015 to ascertain subsequent invasive breast cancer (IBC); cases (n = 218) were women with BBD who developed subsequent IBC and controls, individually matched (1:1) to cases, were women with BBD who did not develop IBC in the same follow-up interval as that for the corresponding case. Targeted sequence capture and sequencing were performed for 83 genes of importance in breast cancer. RESULTS: There were no significant case-control differences in mutation burden overall, for non-silent mutations, for individual genes, or with respect either to the nature of the gene mutations or to mutational enrichment at the pathway level. For seven subjects with DNA from the BBD and ipsilateral IBC, virtually no mutations were shared. CONCLUSIONS: This study, the first to use a targeted multi-gene sequencing approach on early breast cancer precursor lesions to investigate the genomic basis of the disease, showed that somatic mutations detected in BBD tissue were not associated with breast cancer risk.

Missed Opportunities for HIV Prevention: Individuals Who HIV Seroconverted Despite Accessing Healthcare.

Individuals with a negative HIV test before a positive one (seroconverters) may represent missed opportunities for prevention. To inform HIV prevention strategies, we aimed to characterize patients who seroconverted despite accessing care. We identified patients at a large, urban healthcare system who seroconverted between 2009 and 2014. Demographics, visits, and HIV-related variables were extracted from the medical records. We performed descriptive statistics, assessed for trends, and tested for associations according to sex. 220 seroconverters were identified: 45% were female, 87% were non-Hispanic Black or Hispanic, and median number of negative tests prior to diagnosis was 2 (IQR 1-3). Overall, 49% reported heterosexual contact as their risk factor and the proportion with heterosexual risk increased over time (24% in 2009 vs. 56% in 2014, p = 0.03). Compared to men, women were older at the time of diagnosis (35 vs. 26 years old, p < 0.01), had more visits between their latest negative and positive HIV test (4 vs. 2, p < 0.01), and were more likely to be diagnosed in the context of screening (64% vs. 56%, p = 0.05). We identified a population that became HIV-infected despite multiple healthcare encounters and undergoing HIV testing multiple times. Patients were mostly heterosexual and almost half were female. To avoid missed opportunities for those already accessing care, HIV prevention efforts should include strategies tailored to individuals with less frequently recognized risk profiles.

Correction to: Association between lifestyle, menstrual/reproductive history, and histological factors and risk of breast cancer in women biopsied for benign breast disease.

The third category for extent of involution in Table 4 was published incorrectly in the original publication. The correct classification is ≥ 75% and the corrected Table 4 is given in the Correction article.