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This retrospective study at the University of Texas MD Anderson Cancer Center evaluated frontline venetoclax combination therapy in 11 pediatric/adolescent patients with acute myeloid leukemia (AML). Despite the small sample size and retrospective nature, the treatment demonstrated safety and potential efficacy, with most patients achieving early complete remission. Adverse events were consistent with other AML therapies, and no discontinuations due to toxicity occurred. While acknowledging study limitations, including selection bias and diverse concurrent therapies, this research underscores the promising role of venetoclax in pediatric AML. Further investigation is crucial to validate its long-term efficacy in this population.
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BACKGROUND: The long-term financial impact of cancer care has not been adequately addressed in young adults (YAs). As part of a remote intervention study, we describe medical financial distress and hardship of YA survivors of blood cancer at study entry. METHODS: YAs were recruited from six United States hospitals. Via a REDCap™ link, YAs confirmed eligibility: currently 18-39, blood cancer diagnosis ≥3 years ago, off active treatment, and not on parent's insurance. Following consent, the baseline assessment was sent. The primary outcome measure, the Personal Financial Wellness (PFW) Scale, measured financial distress (scored: 1-2 severe, 3-4 high, 5-6 average, 7-10 low-to-no). Medical financial hardship encompassed material hardship, psychological impact, and coping behaviors. Descriptive summary statistics and linear regression were used. RESULTS: The 126 participants consisted of 54.5% minority racial/ethnic representation. Median time since diagnosis was 10 years (IQR, 6-16), with 56% diagnosed between the ages of 18-39. Overall mean PFW score was 5.1 (SD = 2.4), however 49% reported severe or high distress. In multivariable analysis, female sex, Hispanic ethnicity, and lower income were significantly associated with worse PFW scores. Among participants with severe financial distress (n = 26), 72% reported ≥2 household material hardships, had worse scores across all psychological domains, and altered survivorship care due to cost (68%). DISCUSSION: Nearly half of long-term YA survivors reported severe or high levels of financial distress. YAs in severe or high distress also reported more medical financial hardship than other participants. This highlights the need for ongoing financial intervention in this vulnerable population. CLINICALTRIALS.GOV: NCT05620979.
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PURPOSE: Survivors of adolescent and young adult (AYA) cancer face significant psychological distress and encounter barriers accessing mental health care. However, limited research exists on psychological health among lesbian, gay, and bisexual (LGB) survivors of AYA cancer, particularly in comparison with heterosexual survivors and LGB individuals without a history of cancer. METHODS: Using the National Health Interview Survey (2013-2018), we identified LGB survivors of AYA cancer, LGB individuals without a history of cancer, and heterosexual survivors of AYA cancer. Sociodemographic, chronic health conditions, modifiable factors (such as smoking and alcohol use), and psychological outcomes were assessed using chi-square tests. Logistic regression models, adjusted for survey weights, evaluated the odds of psychological distress by cancer status after accounting for covariates. Interactions between variables and cancer status were explored. RESULTS: The study comprised 145 LGB survivors, 1450 LGB individuals without a history of cancer, and 1450 heterosexual survivors. Compared to heterosexual survivors, LGB survivors were more likely to report severe distress (aOR = 2.26, p = 0.021) and had higher odds of reporting a mental health care visit (aOR = 1.98, p = 0.003). Odds of severe distress (aOR = 1.36, p = 0.36) and reporting a mental health care visit (aOR = 1.27, p = 0.29) were similar between LGB survivors and LGB individuals without a history of cancer. While 47.8% of LGB survivors reported moderate/severe distress, only 29.7% reported a mental health care visit. CONCLUSION: A history of cancer during the AYA years is associated higher odds of severe psychological distress among LGB survivors compared to heterosexual survivors. However, many LGB survivors with psychological distress have not accessed mental health care.
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Sobreviventes de Câncer , Angústia Psicológica , Minorias Sexuais e de Gênero , Humanos , Feminino , Masculino , Adulto Jovem , Adolescente , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto , Neoplasias/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Serviços de Saúde Mental/estatística & dados numéricos , Estresse Psicológico/epidemiologiaRESUMO
Purpose: Fertility concerns (FC) are central to the well-being of many adolescent and young adult (AYA) cancer survivors. Clinical conversations about FC and fertility preservation are suboptimal, increasing patient distress. The goal of this project was to establish content validity and comprehensibility of self-report questions on FCs for AYAs with cancer. Methods: Following best practices, we conducted: (1) item identification, refinement, and generation; (2) translatability and reading level review; and (3) cognitive interviews. Items were reviewed by five AYAs in each round of cognitive interviews. Results: A systematic search yielded 63 measures and 873 items. Fifty items were subsequently modified to enhance clarity and relevance, representing subdomains of psychological and social/relational FC. Flesch-Kincaid analysis found 31 items written above the 6th grade level, which were subsequently revised. Translatability review resulted in the modification of 3 items. During cognitive interviews, 76% of AYAs found items easy to answer with 52% describing them as "very easy" and 24% as "somewhat easy." Sixty percent of participants indicated the items captured their experiences. The majority of those who reported items only somewhat reflected or did not reflect their experiences suggested items were simply not applicable for their particular case. Conclusion: This study is a critical step toward the foundation for an FC measurement system that is reliable, flexible, developmentally appropriate, comprehensible, translatable, and interpretable. Subsequent steps include psychometric testing to examine the construct validity and reliability of the FC items and calibration to enable the application of computer-adaptive testing and short form development. The evaluation will include potential item response bias by age range, gender identity, and race/ethnicity.
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There is a known genetic susceptibility to anthracycline-induced cardiac dysfunction in childhood cancer survivors, but this has not been adequately shown in adolescent and young adult (AYA) patients. Our aim was to determine if the previously identified variants associated with cardiac dysfunction in childhood cancer patients affect AYA cancer patients similarly. Forty-five variants were selected for analysis in 253 AYAs previously treated with anthracyclines. We identified four variants that were associated with cardiac dysfunction: SLC10A2:rs7319981 (p = 0.017), SLC22A17:rs4982753 (p = 0.019), HAS3:rs2232228 (p = 0.023), and RARG:rs2229774 (p = 0.050). HAS3:rs2232228 and SLC10A2:rs7319981 displayed significant effects in our AYA cancer survivor population that were in the opposite direction than that reported in childhood cancer survivors. Genetic variants in the host genes were further analyzed for additional associations with cardiotoxicity in AYA cancer survivors. The host genes were then evaluated in a panel of induced pluripotent stem cell-derived cardiomyocytes to assess changes in levels of expression when treated with doxorubicin. Significant upregulation of HAS3 and SLC22A17 expression was observed (p < 0.05), with non-significant anthracycline-responsivity observed for RARG. Our study demonstrates that there is a genetic influence on cardiac dysfunction in AYA cancer patients, but there may be a difference in the role of genetics between childhood and AYA cancer survivors.
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Antraciclinas , Sobreviventes de Câncer , Cardiotoxicidade , Predisposição Genética para Doença , Humanos , Adolescente , Antraciclinas/efeitos adversos , Adulto Jovem , Masculino , Feminino , Cardiotoxicidade/genética , Adulto , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Cardiopatias/induzido quimicamente , Cardiopatias/genética , Antibióticos Antineoplásicos/efeitos adversos , Fatores de RiscoRESUMO
Evidence suggests neighborhood-level factors contribute to cancer outcomes, though most research focuses on pediatric and adult populations. Using population-based data from the Texas Cancer Registry, we examined neighborhood-level social vulnerability, a composite measure of 14 census tract-level social risk factors, and survival among 112,142 adolescents and young adults with cancer (AYAs, age 15-39 years). We estimated one-, five-, and ten-year overall survival by quintile of social vulnerability and used Cox proportional hazards models (two-sided significance testing) to estimate the association between social vulnerability and all-cause mortality. Survival decreased as social vulnerability increased; for example, five-year survival was 86.5% (95% CI 85.1, 87.0) in the least vulnerable quintile compared to 74.0% (95% CI 73.4, 74.5) in the most vulnerable quintile. Social vulnerability was associated with all-cause mortality in adjusted models (highest vs lowest quintile: aHR 1.55, 95% CI 1.48, 1.63). Achieving equity in AYAs' survival requires interventions to address neighborhood disparities.
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BACKGROUND: The overall landscape of health-related quality of life (HRQoL) has not been thoroughly investigated in adolescents and young adults (AYAs) with cancer. Data are also lacking on how well HRQoL at the time of cancer diagnosis can prognosticate long-term survival in AYA survivors. PATIENTS AND METHODS: We included 3,497 survivors of AYA cancer (age 15-39 years at diagnosis) who completed the Short-Form 12 Health Survey (SF-12) HRQoL questionnaire at diagnosis. Physical component summary (PCS) and mental component summary (MCS) scores were generated, with scores <50 representing poor HRQoL. Differences in HRQoL by patient characteristics and tumor type were investigated using violin plots and t tests/analysis of variance. The effect of HRQoL on overall survival was assessed using Kaplan-Meier plots and Cox proportional hazards models. RESULTS: Overall mean PCS and MCS scores in this racially/ethnically diverse cohort (64% White, 19% Hispanic, 10% Black, and 7% other race/ethnicity) were 43.6 and 46.7, respectively. Women with breast cancer reported the most favorable PCS (50.8), and those with cervical cancer reported the lowest MCS (42.8). Age at diagnosis was associated positively with PCS (P<.001) and inversely with MCS (P<.001). Females had higher PCS yet lower MCS than males (both P<.001). Marginalized racial and ethnic populations reported lower PCS than White patients (P<.001). Physical and mental HRQoL were prognostic and associated with increased risk of poor survival (hazard ratio, 1.95; 95% CI, 1.72-2.21 for physical HRQoL, and 1.26; 95% CI, 1.13-1.40 for mental HRQoL). CONCLUSIONS: Physical and mental HRQoL at diagnosis vary across patient characteristics in AYA cancer survivors. Poor HRQoL at diagnosis may be a prognosticator of diminished overall survival among AYA cancer survivors.
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Neoplasias , Qualidade de Vida , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Neoplasias/psicologia , Neoplasias/diagnóstico , Neoplasias/mortalidade , Adulto , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , PrognósticoRESUMO
BACKGROUND: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer. METHODS: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10â261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH. RESULTS: ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043). CONCLUSION: Adolescent and young adult patients with cancer and the worst ADI values experienced a nearly 10% increase in risk of dying than patients with more favorable ADI values. This effect was strongest among White adolescent and young adult survivors. Although the magnitude of the effect of ADI on survival was moderate, the presence of a relationship between neighborhood-level SDOH and survival among patients who received care at a tertiary cancer center suggests that ADI is a meaningful predictor of survival. These findings provide intriguing evidence for potential interventions aimed at supporting adolescent and young adult patients with cancer from disadvantaged neighborhoods.
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Hispânico ou Latino , Neoplasias , Determinantes Sociais da Saúde , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Neoplasias/mortalidade , Hispânico ou Latino/estatística & dados numéricos , População Branca/estatística & dados numéricos , Características da Vizinhança , Negro ou Afro-Americano/estatística & dados numéricos , Adulto , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/etnologia , Modelos de Riscos Proporcionais , Características de Residência , Fatores SocioeconômicosRESUMO
INTRODUCTION: Improving health care quality and patient safety are top priorities for the medical field. Robust continuing medical education (CME) programs represent major interventions to effectively teach quality improvement (QI) principles to practicing physicians. In particular, eLearning, a term describing online and distance learning interventions using digital tools, provides a means for CME interventions to reach broader audiences. Although there has been a focus on CME addressing QI, no knowledge synthesis has focused specifically on eLearning interventions. The purpose of this review was to examine the current landscape of eLearning interventions in QI-focused CME. METHODS: We conducted a scoping review using the framework developed by Arksey and O'Malley as revised by Levac. We searched five databases and identified 2467 prospective publications, which two authors independently screened for inclusion. From each included article, two authors independently extracted data on the instructional modalities and QI tools used and met regularly to achieve consensus. RESULTS: Twenty-one studies were included. Most studies used blended instruction (n = 12) rather than solely eLearning interventions. Salient findings included the importance of coaching from QI experts and institutional support for planning and implementing eLearning interventions. Lack of protected time and resources for participants were identified as barriers to participation in CME activities, with small practices being disproportionately affected. DISCUSSION: Partnerships between CME developers and sponsoring organizations are vital in creating sustainable eLearning interventions for QI-focused CME. Remote coaching can be an effective strategy to provide ongoing support to geographically separated learners.
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Purpose: Financial hardship as a result of cancer treatment can have a significant and lasting negative impact on adolescents and young adults (AYAs) and their families. To address a lack of developmentally informed and psychometrically sound measures of financial hardship for AYAs and their caregivers, we used rigorous measurement development methods recommended by the National Institutes of Health's Patient-Reported Outcomes Measurement Information System® (PROMIS®) to determine comprehensibility and relevance of measure content. Methods: Our multi-step approach involved item identification, refinement, and generation; translatability and reading level review; and cognitive interviews. A purposive sample of 25 AYAs and 10 caregivers participated, ensuring representation across age, education, gender, race/ethnicity, and cancer type. Results: Fifty patient-reported and caregiver-reported items were developed across material, psychosocial, and behavioral subdomains of financial hardship. Translatability and reading level reviews resulted in 22 patient-reported and 25 caregiver-reported items being rewritten. Eighty-eight percent of patients and all caregivers described the items as easy to answer. Younger AYAs (15 to 25 years of age) were more likely to say the items were less relevant for them. Forty-six patient-reported and 48 caregiver-reported items were recommended for further testing. Conclusion: This study is the first to use in-depth qualitative methods to center AYA patient and caregiver experiences in the creation of new measures of financial hardship. Data support the comprehensibility and content validity of these preliminary item banks. Future large-scale, quantitative testing will lead to additional refinements and support the use of short forms and computer-adaptive testing for a diverse sample of AYAs and their caregivers.
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Survivors of adolescent and young adult (AYA, age 15-39 years at diagnosis) cancer are a growing population with the potential to live for many decades after treatment completion. Survivors of AYA cancer are at risk for adverse long-term outcomes including chronic conditions, secondary cancers, impaired fertility, poor psychosocial health and health behaviors, and financial toxicity. Further, survivors of AYA cancer from racially minoritized and low socio-economic status populations experience disparities in these outcomes, including lower long-term survival. Despite these known risks, most survivors of AYA cancer do not receive routine survivorship follow-up care, and research on delivering high-quality, evidence-based survivorship care to these patients is lacking. The need for survivorship care was initially advanced in 2006 by the Institute of Medicine. In 2019, the Quality of Cancer Survivorship Care Framework (QCSCF) was developed to provide an evidence-based framework to define key components of optimal survivorship care. In this commentary focused on survivors of AYA cancer, we apply the QCSCF framework to describe models of care that can be adapted for their unique needs, multi-level factors limiting equitable access to care, and opportunities to address these factors to improve short- and long-term outcomes in this vulnerable population.
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Ataxia Telangiectasia , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Sulfonamidas , Humanos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/complicações , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Masculino , Antineoplásicos/uso terapêutico , Feminino , CriançaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Doença de Hodgkin , Nivolumabe , Humanos , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/terapia , Doença de Hodgkin/patologia , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Criança , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Feminino , Antineoplásicos Imunológicos/uso terapêutico , Adolescente , Imunoterapia/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/uso terapêuticoRESUMO
Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor ß1 (TGF-ß1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-ß1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-ß1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.
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INTRODUCTION: Fertility after cancer is a top concern for adolescents and young adults with cancer (AYAs) (15-39 years old at diagnosis). The authors characterized live births after cancer by race and ethnicity ("race/ethnicity") in a population-based sample of female AYAs. METHODS: This study used Texas Cancer Registry data linked to birth certificates (1995-2016) to estimate cumulative incidence of live birth, based on first live birth after cancer, and compared differences by race/ethnicity. Proportional subdistribution hazards models were used to estimate associations between race/ethnicity and live birth, adjusted for diagnosis age, cancer type, stage, year, and prior live birth, overall and for each cancer type. RESULTS: Among 65,804 AYAs, 10-year cumulative incidence of live birth was lower among non-Hispanic Black AYAs than other racial/ethnic groups: 10.2% (95% confidence interval [CI], 9.4-10.9) compared to 15.9% (95% CI, 14.1-17.9) among Asian or Pacific Islander, 14.7% (95% CI, 14.2-15.3) among Hispanic, and 15.2% (95% CI, 14.8-15.6) among non-Hispanic White AYAs (p < .01). In the adjusted overall model, Black AYAs were less likely to have a live birth after cancer than all other groups. In adjusted models for each cancer type, live birth was significantly less likely for Black AYAs with gynecologic cancers or lymphomas (compared to White AYAs) or thyroid cancers (compared to Hispanic AYAs). CONCLUSION: Black AYAs are less likely than AYAs of other races/ethnicities to have a live birth after cancer, in contrast to patterns of live birth in the general population. Research and action to promote childbearing equity after cancer are imperative.
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Sobreviventes de Câncer , Nascido Vivo , Neoplasias , Adolescente , Adulto , Feminino , Humanos , Adulto Jovem , Negro ou Afro-Americano/estatística & dados numéricos , Sobreviventes de Câncer/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Incidência , Nascido Vivo/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etnologia , Sistema de Registros , Texas/epidemiologia , Brancos/estatística & dados numéricosRESUMO
BACKGROUND: Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients' response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro. METHODS: Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRß and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10- 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation. RESULTS: Expression of GR and its isoform GRα but not GRß was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRß between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p < 0.0001) as compared to non-responders. CONCLUSIONS: These data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5. TRIAL REGISTRATION: ISRCTN11017699 (Registration date: 15/11/2016).
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Histona Desacetilases , Miócitos de Músculo Liso , Doença Pulmonar Obstrutiva Crônica , Receptores de Glucocorticoides , Humanos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/biossíntese , Histona Desacetilases/metabolismo , Histona Desacetilases/biossíntese , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Células Cultivadas , Corticosteroides/uso terapêutico , Glucocorticoides/farmacologia , Dexametasona/farmacologia , Resultado do Tratamento , Administração por Inalação , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Brônquios/enzimologiaRESUMO
BACKGROUND: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population. METHODS: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate the odds of psychological distress by cancer status after adjusting for covariates. Interactions between variables and cancer status were investigated. RESULTS: The study included 334 Black survivors of AYA cancer and 3340 Black controls. Compared to controls, survivors were more likely to report moderate/severe distress (odds ratio [OR], 1.64; p < .001), use mental health care (OR, 1.53; p = .027), report an inability to afford mental health care (OR, 3.82; p < .001), and use medication for anxiety and/or depression (OR, 2.16; p = .001). Forty-one percent of survivors reported moderate/severe distress, and only 15% used mental health care. Among survivors, ages 18-39 years (vs. 40-64 years) and current smoking (vs. never smoking) were associated with the presence of moderate/severe distress. Among survivors with distress, high poverty status was associated with reduced utilization of mental health care. CONCLUSIONS: A cancer diagnosis for a Black AYA is associated with greater psychological distress within an already vulnerable population.
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Negro ou Afro-Americano , Sobreviventes de Câncer , Angústia Psicológica , Humanos , Feminino , Masculino , Adulto Jovem , Adolescente , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias/psicologia , Neoplasias/terapia , Neoplasias/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Serviços de Saúde Mental/estatística & dados numéricosRESUMO
PURPOSE: The response to glucocorticoids is hampered in many COPD patients by a yet unknown mechanism. Earlier we reported that short-term heat exposure of primary human bronchial epithelial cells (BEC) and airway smooth muscle cells (ASMC) of asthma patients increased the expression and secretion of extracellular heat shock proteins (eHSPs) resulting in increased expression of glucocorticoid receptor (GR) in BEC and inhibition of ASMC remodeling. The aim of the present study was to assess if the same mechanism is also present in primary airway wall cells of COPD patients. METHODS: Primary BEC and ASMC were established from endobronchial biopsies obtained from COPD patients (n = 73), who participated in the HISTORIC study, an investigator-initiated and driven clinical trial. Secretion and protein expression of HSPs was assessed by ELISA and Western blotting. Expression of total GR, its isoforms GRα and GRß and toll-like receptor 4 (TLR4) was determined by Western-blotting. RESULTS: Short heat exposure (65 °C, 10 s) of BEC resulted in a significant increase of the secretion of eHSP70 and eHSP90, while the intracellular protein was not altered. Heat treatment or exposure to eHSP70 or eHSP90 had no effect on the expression of GR and GR-isoforms. However, eHSP70 and eHSP90 significantly reduced the expression of TLR4. CONCLUSIONS: The results of this study indicate that primary airway cells from COPD patients respond differently to heat exposure and extracellular HSP70 or HSP90 than cells from asthma patients regarding the expression of GR and this may explain the reduced response to glucocorticoids in patients with COPD. TRIAL REGISTRATION: ISRCTN11017699.