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BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.
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BACKGROUND: Recent studies have reported a reduction in health-related quality of life (HR-QoL) among post-coronavirus disease 2019 (COVID-19) patients. However, there remains a gap in research examining the heterogeneity and determinants of HR-QoL trajectory in these patients. OBJECTIVE: To describe and identify factors explaining the variability in HR-QoL trajectories among a cohort of patients with history of COVID-19. DESIGN: A prospective study using data from a cohort of COVID-19 patients enrolled into a registry established at a health system in New York City. PARTICIPANTS: Participants were enrolled from July 2020 to June 2022, and completed a baseline evaluation and two follow-up visits at 6 and 12 months. METHODS: We assessed HR-QoL with the 29-item Patient Reported Outcomes Measurement Information System instrument, which was summarized into mental and physical health domains. We performed latent class growth and multinomial logistic regression to examine trajectories of HR-QoL and identify factors associated with specific trajectories. RESULTS: The study included 588 individuals with a median age of 52 years, 65% female, 54% White, 18% Black, and 18% Hispanic. We identified five physical health trajectories and four mental health trajectories. Female gender, having pre-existing hypertension, cardiovascular disease, asthma, and hospitalization for acute COVID-19 were independently associated with lower physical health. In addition, patients with increasing body mass index were more likely to experience lower physical health over time. Female gender, younger age, pre-existing asthma, arthritis and cardiovascular disease were associated with poor mental health. CONCLUSIONS: We found significant heterogeneity of HR-QoL after COVID-19, with women and patients with specific comorbidities at increased risk of lower HR-QoL. Implementation of targeted psychological and physical interventions is crucial for enhancing the quality of life of this patient population.
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COVID-19 , Calidad de Vida , Humanos , Calidad de Vida/psicología , Femenino , Masculino , COVID-19/psicología , COVID-19/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Ciudad de Nueva York/epidemiología , Anciano , SARS-CoV-2 , Estado de Salud , Salud MentalRESUMEN
PURPOSE: To describe differences in post-traumatic stress (PTS) symptoms over time among racial and ethnic minoritized breast cancer survivors (BCS) with comorbid diabetes. DESIGN: In a multisite longitudinal study, post-traumatic stress was evaluated at baseline, 6 and 12 months through self-reported questionnaires (Impact of Events Scale-Revised [IES-R]). PARTICIPANTS: One hundred and seventy-eight post-treatment BCS with diabetes were recruited from three tertiary medical centers. FINDINGS: Relative to non-Hispanic White women, minoritized women reported higher total IES-R scores at all time points. In the adjusted model, Latina women reported persistently higher IES-R total scores and Latina, and 'Other' women reported higher avoidance scores. CONCLUSIONS: Minoritized BCS with comorbid diabetes report higher rates of cancer related PTS that persist over 12 months. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Post diagnosis PTS evaluation and support is important in survivorship and primary care practices. Linkage to socially and culturally sensitive community support may be warranted.
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Neoplasias de la Mama , Supervivientes de Cáncer , Diabetes Mellitus , Trastornos por Estrés Postraumático , Humanos , Femenino , Supervivientes de Cáncer/psicología , Neoplasias de la Mama/psicología , Estudios Longitudinales , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
Among Asian Americans, cancer is the leading cause of death and colorectal cancer (CRC) is the second most common cancer.1 The uptake of CRC screening influences incidence and mortality trends; however, the most recent American Cancer Society CRC statistics reveals ongoing disparities in screening based on race and ethnicity, with people of Asian descent demonstrating the lowest CRC screening rates despite being the fastest growing racial or ethnic group in the United States.2,3.
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Asiático , Neoplasias Colorrectales , Humanos , Estados Unidos/epidemiología , Incidencia , Etnicidad , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Detección Precoz del CáncerRESUMEN
BACKGROUND: The COVID-19 pandemic has necessitated a rapid uptake of telemedicine in primary care requiring both patients and providers to learn how to navigate care remotely. This change can impact the patient-provider relationship that often defines care, especially in primary care. OBJECTIVE: This study aims to provide insight into the experiences of patients and providers with telemedicine during the pandemic, and the impact it had on their relationship. RESEARCH DESIGN: A qualitative study using thematic analysis of semistructured interviews. SUBJECTS: Primary care providers (n=21) and adult patients (n=65) with chronic disease across primary care practices in 3 National Patient-centered Clinical Research Network sites in New York City, North Carolina, and Florida. MEASURES: Experiences with telemedicine during the COVID-19 pandemic in primary care. Codes related to the patient-provider relationship were analyzed for this study. RESULTS: A recurrent theme was the challenge telemedicine posed on rapport building and alliance. Patients felt that telemedicine affected provider's attentiveness in varying ways, whereas providers appreciated that telemedicine provided unique insight into patients' lives and living situations. Finally, both patients and providers described communication challenges. CONCLUSIONS: Telemedicine has altered structure and process aspects of primary health care such as the physical spaces of encounters, creating a new setting to which both patients and providers must adjust. It is important to recognize the opportunities and limits that this new technology has to help providers maintain the type of one-on-one attention that patients expect and that contributes to relationship building.
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COVID-19 , Telemedicina , Adulto , Humanos , Pandemias , Relaciones Profesional-Paciente , Atención Primaria de SaludRESUMEN
BACKGROUND: A number of patients post-coronavirus disease-19 (COVID-19) report cognitive impairment (CI), even months after acute infection. We aimed to assess if COVID-19 is associated with increased incidence of CI in comparison to controls. METHODS: We analyzed data from the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort of patients post-COVID-19 ≥18 years of age and non-infected controls. CI was defined by scores ≥ 1.0 standard deviation below population norms, and was assessed using well-validated measures of attention, working memory, processing speed, executive functioning/cognitive flexibility, language, learning, and memory. Logistic regression models assessed odds for CI in each domain in patients post-COVID-19 vs. controls after adjusting for potential confounders. In exploratory analyses, we assessed odds for CI by site of acute COVID-19 care as a proxy for disease severity. FINDINGS: 417 patients post-COVID-19 and 151 controls (mean age 49 years, 63% female, 21% Black, 17% Latinx) were included. In adjusted analyses, patients were significantly more likely than controls to have CI in executive functioning (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.03 to 4.67), particularly those treated in outpatient (OR: 2.22; 95% CI: 1.02 to 4.82) and inpatient hospital (OR: 3.59; 95% CI: 1.27 to 10.16) settings. There were no significant associations between CI in other domains and history of COVID-19 or site of acute care. INTERPRETATION: Patients post-COVID-19 have greater odds of executive dysfunction, suggesting that focused cognitive screening may be prudent, even in those with mild to moderate disease. Studies should explore the pathophysiology and potential treatments for CI in this population. FUNDING: This work was funded by the Icahn School of Medicine at Mount Sinai.
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COVID-19 , Disfunción Cognitiva , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , COVID-19/complicaciones , Disfunción Cognitiva/etiología , Función Ejecutiva/fisiología , AprendizajeRESUMEN
PURPOSE: The need to rapidly implement telemedicine in primary care during the coronavirus disease 2019 (COVID-19) pandemic was addressed differently by various practices. Using qualitative data from semistructured interviews with primary care practice leaders, we aimed to report commonly shared experiences and unique perspectives regarding telemedicine implementation and evolution/maturation since March 2020. METHODS: We administered a semistructured, 25-minute, virtual interview with 25 primary care practice leaders from 2 health systems in 2 states (New York and Florida) included in PCORnet, the Patient-Centered Outcomes Research Institute clinical research network. Questions were guided by 3 frameworks (health information technology evaluation, access to care, and health information technology life cycle) and involved practice leaders' perspectives on the process of telemedicine implementation in their practice, with a specific focus on the process of maturation and facilitators/barriers. Two researchers conducted inductive coding of qualitative data open-ended questions to identify common themes. Transcripts were electronically generated by virtual platform software. RESULTS: Twenty-five interviews were administered for practice leaders representing 87 primary care practices in 2 states. We identified the following 4 major themes: (1) the ease of telemedicine adoption depended on both patients' and clinicians' prior experience using virtual health platforms, (2) regulation of telemedicine varied across states and differentially affected the rollout processes, (3) visit triage rules were unclear, and (4) there were positive and negative effects of telemedicine on clinicians and patients. CONCLUSIONS: Practice leaders identified several challenges to telemedicine implementation and highlighted 2 areas, including telemedicine visit triage guidelines and telemedicine-specific staffing and scheduling protocols, for improvement.
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COVID-19 , Telemedicina , Humanos , Estados Unidos , COVID-19/epidemiología , Telemedicina/métodos , New York , Atención Primaria de SaludRESUMEN
BACKGROUND: Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care. METHODS: In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20-25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items. RESULTS: Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., "maturation". Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction. CONCLUSION: This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset.
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COVID-19 , Telemedicina , Humanos , Estados Unidos , COVID-19/epidemiología , Telemedicina/métodos , Encuestas y Cuestionarios , Pandemias , Atención Primaria de SaludRESUMEN
Clinical rotations are often not included in graduate-level cancer biology curricula; however, basic insight into clinical oncology is often crucial for developing translational research that addresses unmet needs with the potential to benefit cancer patients. We describe a needs assessment, design, implementation, and descriptive evaluation of an oncology-specific pilot clinical encounter program developed for PhD students in the Cancer Biology Training Area (CAB) in the Graduate School of Biomedical Sciences (GSBS) and Tisch Cancer Institute (TCI) at the Icahn School of Medicine at Mount Sinai (ISMMS). Prior to the development of this pilot program, CAB students, in years 2-5 + , were surveyed to determine their interest in a structured clinical experience. Seventeen out of thirty-one students responded (55%) to the survey. Of those seventeen respondents, fifteen (88.2%) expressed that exposure to cancer patients in the clinical setting would be useful for their pre-doctoral biomedical science and cancer biology training and indicated an interest in participating in the clinical encounter program. Based on these responses, a three-session clinical encounter pilot program was designed. Two separate cohorts of 5 students participated in this pilot program. During a formal debrief, following the clinical experience, students commented on the resilience of patients and the importance of research on clinical decision making, and reported that they found the experience motivational. Five out of 10 students responded (50%) to a post-program assessment survey; all five respondents answered that they would recommend the clinical encounter program to their peers. While limited in size and scope, this pilot TCI Clinical Encounter Program proved feasible and has the potential to enrich and inform the experience of PhD students pursing advanced degrees in a cancer biology.
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Neoplasias , Estudiantes , Humanos , Estudios de Factibilidad , Educación de Postgrado , BiologíaRESUMEN
BACKGROUND: Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective cohort to assess differences in post-acute sequelae of COVID (PASC) among vaccinated vs. unvaccinated patients. METHODS: We used data from a cohort of COVID-19 patients enrolled into a prospective registry established at a tertiary care health system in New York City. Participants underwent a baseline evaluation before COVID-19 vaccines were available and were followed 6 months later. We compared unadjusted and propensity score-adjusted baseline to 6-month change for several PASC-related symptoms and measures: anosmia, respiratory (cough, dyspnea, phlegm, wheezing), depression, anxiety, post-traumatic stress disorder (PTSD; COVID-19-related and other trauma), and quality-of-life domains among participants who received vs. those who did not receive COVID-19 vaccination. RESULTS: The study included 453 COVID-19 patients with PASC, of which 324 (72%) were vaccinated between the baseline and 6-month visit. Unadjusted analyses did not show significant differences in the baseline to 6-month change in anosmia, respiratory symptoms, depression, anxiety, PTSD, or quality of life (p > 0.05 for all comparisons) among vaccinated vs. unvaccinated patients. Similar results were found in propensity-adjusted comparisons and in secondary analyses based on the number of vaccine doses received. CONCLUSIONS: Our findings suggest that COVID vaccination is not associated with improvement in PASC. Additional studies are needed to better understand the mechanisms underlying PASC and to develop effective treatments.
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COVID-19 , SARS-CoV-2 , Anosmia , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Progresión de la Enfermedad , Humanos , Calidad de Vida , VacunaciónRESUMEN
Cancer research has led to unprecedented advances in treatment in recent decades. Physician-scientists have played a crucial role in these advances given their unique perspective at the intersection between basic research and clinical care, though their representation in cancer research has been in progressive decline. Cancer research programs that feature strong mentorship at the medical student level are associated with increased likelihood of alumni choosing a cancer research career path. In an effort to increase the cancer research medical student training pipeline, senior research faculty from the Tisch Cancer Institute (TCI) at the Icahn School of Medicine at Mount Sinai (ISMMS) developed the TCI Scholars Program, a rigorous mentored research training program funding medical students' summer research. This program is currently in its third year and has garnered significant interest among mentors and students alike from all four TCI Cancer Center Support Grant (CCSG)-funded research programs. Herein, we describe the development, implementation, evaluation, and major outcomes of this program.
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Investigación Biomédica , Neoplasias , Estudiantes de Medicina , Academias e Institutos , Investigación Biomédica/educación , Docentes , Humanos , Mentores , Neoplasias/prevención & control , Evaluación de Programas y Proyectos de SaludRESUMEN
CONTEXT: Breast cancer survivors (BCS) with comorbid diabetes mellitus (DM) and of racial and ethnic minority status are at higher risk of cancer-related post-traumatic stress (PTS) and severe illness beliefs. These affective and cognitive outcomes influence self-management and treatment adherence in patients with chronic conditions, yet little is known regarding the interplay of these processes in diverse BCS with comorbid DM. OBJECTIVES: The purposes of this study were to (1) describe racial and ethnic differences in cancer-related PTS and illness perceptions; and (2) examine the relationship between PTS and illness perceptions in BCS with comorbid DM. METHODS: Female BCS with DM completed measures of cancer related stress (Impact of Events Scale-Revised) and cancer and DM illness perception (Illness Perception Questionnaire-Revised). Logistic regression analyses were used to assess the association between PTS, race and illness perceptions. RESULTS: Of the 135 BCS with comorbid DM, the mean (standard deviation) age was 65.3 (7.1) years, 38% were Black, 31% Non-Hispanic White (NHW), 13% Hispanic/Latina, and 18% were "other." Minority women were more likely to report cancer-related PTS (p < 0.01). In adjusted analyses, PTS was associated with chronicity (odds ratio [OR] = 9.79, p = 0.005), time-cycle (OR = 6.71, p = 0.001), negative consequences (OR = 3.95, p = 0.018), and negative emotional impact (OR = 12.63, p < 0.001) of cancer. CONCLUSION: Minority BCS with comorbid DM report higher rates of cancer-related PTS and lower cancer illness coherence relative to NHW survivors. Cancer-related PTS influences cancer and DM illness perceptions. Culturally sensitive care is needed to improve these outcomes in minority BCS. KEY MESSAGE: This article presents findings from a cross sectional cohort of an understudied population of racially and ethnically diverse BCS with comorbid diabetes. The results indicate that the occurrence of PTS is significantly higher in racial and ethnic minority women and is strongly associated with more severe illness perceptions.
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Neoplasias de la Mama , Supervivientes de Cáncer , Diabetes Mellitus , Trastornos por Estrés Postraumático , Anciano , Neoplasias de la Mama/epidemiología , Estudios Transversales , Diabetes Mellitus/epidemiología , Etnicidad , Femenino , Hispánicos o Latinos , Humanos , Grupos Minoritarios , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.
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Neoplasias de la Mama , Supervivientes de Cáncer , Disfunción Cognitiva , Anciano , Cognición , Femenino , Humanos , SobrevivientesRESUMEN
The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR. However, these widely used strategies activate TCRs through a nonphysiological mechanism and can produce different activation profiles than natural, monovalent, membrane-associated pMHC. Here, we introduce a strictly monovalent anti-TCRß H57 Fab' ligand that, when coupled to a supported lipid bilayer via DNA complementation, triggers TCRs and activates nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT) with a similar potency to pMHC in primary murine T cells. Importantly, like monovalent pMHC and unlike bivalent antibodies, monovalent Fab'-DNA triggers TCRs only when physically coupled to the membrane, and only around 100 individual Fab':TCR interactions are necessary to stimulate early T cell activation.
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Activación de Linfocitos , Receptores de Antígenos de Linfocitos T , Animales , Ligandos , Complejo Mayor de Histocompatibilidad , Ratones , Linfocitos TRESUMEN
BACKGROUND: Mammography is limited when analyzing dense breasts for 2 reasons: (1) breast density masks underlying cancers and (2) breast density is an independent risk factor for cancer. We undertook this study to assess whether there is a racial/ethnic difference in supplemental image ordering for women with dense breasts. METHODS: We conducted a retrospective, observational cohort study of women aged 50-75 from an academic medical center who had completed a screening mammogram between 2014 and 2016 that was read as BI-RADS 1 with heterogeneously or extremely dense breasts or BI-RADS 2 with extremely dense breasts. Data were abstracted on type, timing and frequency of supplemental imaging tests ordered within two years of an initial screening mammogram. Patient characteristics (age, race/ethnicity, insurance, and comorbidities) were also abstracted. We used bivariate and multivariate logistic regression to assess for differences in supplemental imaging ordered by race/ethnicity. RESULTS: Three hundred twenty-six women met inclusion criteria. Mean age was 58 years: 25% were non-Hispanic white, 30% were non-Hispanic black, 27% were Hispanic, 6% were Asian and 14% unknown. Seventy-nine (24%) women were ordered a supplemental breast ultrasound after the initial screening mammogram. Non-Hispanic black and Hispanic women were less likely to have supplemental imaging ordered compared to non-Hispanic white women (15% and 10%, respectively, vs. 45%, p < 0.0001). After controlling for patient age, ordering physician specialty, insurance, BI-RADS score, breast density, and family history of breast cancer, non-Hispanic black and Hispanic women remained less likely to be ordered supplemental imaging (OR 0.38 [95% CI 0.17-0.85] and OR 0.24 [95% CI 0.10-0.61], respectively, p < 0.0001). CONCLUSION: Minority women with dense breasts are less likely to be ordered supplemental breast imaging. Further research should investigate physician and patient behaviors to determine barriers in supplemental imaging. Understanding these differences may help reduce disparities in breast cancer care and mortality.
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Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Disparidades en Atención de Salud , Mamografía/estadística & datos numéricos , Ultrasonografía Mamaria/estadística & datos numéricos , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Antigen discrimination by T cells occurs at the junction between a T cell and an antigen-presenting cell. Juxtacrine binding between numerous adhesion, signaling, and costimulatory molecules defines both the topographical and lateral geometry of this cell-cell interface, within which T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interact. These physical constraints on receptor and ligand movement have significant potential to modulate their molecular binding properties. Here, we monitor individual ligand:receptor binding and unbinding events in space and time by single-molecule imaging in live primary T cells for a range of different pMHC ligands and surface densities. Direct observations of pMHC:TCR and CD80:CD28 binding events reveal that the in situ affinity of both pMHC and CD80 ligands for their respective receptors is modulated by the steady-state number of agonist pMHC:TCR interactions experienced by the cell. By resolving every single pMHC:TCR interaction it is evident that this cooperativity is accomplished by increasing the kinetic on-rate without altering the off-rate and has a component that is not spatially localized. Furthermore, positive cooperativity is observed under conditions where the T cell activation probability is low. This TCR-mediated feedback is a global effect on the intercellular junction. It is triggered by the first few individual pMHC:TCR binding events and effectively increases the efficiency of TCR scanning for antigen before the T cell is committed to activation.
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Antígenos/inmunología , Antígeno B7-1/inmunología , Antígenos CD28/inmunología , Complejo Mayor de Histocompatibilidad , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Animales , Antígenos/metabolismo , Antígeno B7-1/genética , Antígenos CD28/genética , Expresión Génica , Ligandos , Membrana Dobles de Lípidos/química , Activación de Linfocitos , Ratones , Cultivo Primario de Células , Unión Proteica , Receptores de Antígenos de Linfocitos T/genética , Transducción de Señal/inmunología , Análisis de la Célula Individual , Linfocitos T/citologíaRESUMEN
BACKGROUND: Despite lower incidence rates among black women and a national decline in breast cancer (BC) deaths, there is a widening gap in BC mortality rates between black and white women in the United States. A previous study evaluating data from 1992 to 1999 found a racial disparity in the receipt of surveillance mammography. We sought to evaluate whether this disparity persists between black and white women diagnosed with BC between 2000 and 2011. METHODS: Using the SEER-Medicare registry, we conducted an analysis of women ≥ 66 years diagnosed with early-stage (0-III) BC between 2000 and 2011 who underwent BC surgery. The primary outcome was receipt of surveillance mammography within 12 months of surgery. Chi square analyses were used to compare characteristics between black and white women. Multivariate logistic regression was used to assess receipt of surveillance mammography after controlling for potential confounders. RESULTS: There were 3353 black and 40,564 white women in the final cohort. After adjusting for confounders, black women were still 24% less likely than white women to receive surveillance mammography (Odds ratio 0.76, 95% CI 0.70-0.0.82). Those who were married, younger, in the highest income quartile, diagnosed at earlier stages, had a lower comorbidity score, or who resided in metropolitan areas were more likely to receive surveillance mammography (p < 0.05). CONCLUSION(S): We found that older black BC survivors continue to experience lower rates of surveillance mammography, even after adjusting for multiple potential confounders. There remains a need to investigate which individual and systemic factors affect disparities in breast cancer care.
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Neoplasias de la Mama/diagnóstico por imagen , Disparidades en Atención de Salud/etnología , Mamografía/métodos , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/etnología , Neoplasias de la Mama/cirugía , Supervivientes de Cáncer , Femenino , Humanos , Vigilancia de la Población , Programa de VERF , Estados Unidos/etnología , Población Blanca/estadística & datos numéricosRESUMEN
In the original publication of the article, under the Methods section, second paragraph, the sentence that reads as "We excluded 3047 patients surgical treatment (see Fig. 1)" should read as "We excluded 3047 patients who did not identify as black or white, 5395 who were not initially diagnosed with stage 0-III cancer or were missing stage or residence data, 2573 patients who passed away within 18 months of diagnosis, and 4716 patients who did not undergo primary surgical treatment (see Fig. 1)".