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1.
Patient Educ Couns ; 123: 108194, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38350208

RESUMO

BACKGROUND: Cancer survivors experience complex medical and psychosocial challenges after a cancer diagnosis, leading to unmet informational and emotional needs. There is a paucity of cancer survivorship educational resources co-created by survivors and medical professionals. OBJECTIVE: Our aim was to create an educational resource for cancer survivors, caregivers, and medical professionals that would leverage digital storytelling to address survivorship topics. PATIENT INVOLVEMENT: Our content and production team included cancer survivors, clinicians, educators, and design experts. All content was co-created by cancer survivors and medical experts. METHODS: We conducted an environmental scan of existing cancer survivorship educational resources in academic and public domains. Applying human-centered design principles, we incorporated patient perspectives through advisory board meetings and focus groups and identified a podcast as the preferred medium. We selected content and speakers, produced the podcast, and developed a corresponding website. RESULTS: Based on patient recommendations, podcast episodes address mental health, fear of cancer recurrence, relationships, parenting, relating to a new body, care transitions for adult survivors of childhood cancer, disclosing health information, and financial burden of cancer. Podcast guests were invited based on lived or learned experience in these domains. Thirteen guests (survivors, experts) and four hosts (two cancer survivors, two oncologists) co-created 15 podcast episodes. Podcast guests found the storytelling experience to be powerful and therapeutic. DISCUSSION: Digital storytelling is a scalable and accessible educational tool for communicating complex survivorship concepts that can amplify survivors' voices and increase awareness among survivors and clinicians. Co-creation of educational resources for cancer survivorship by survivors and professionals is a feasible and innovative educational strategy. PRACTICAL VALUE: A podcast created by and for cancer survivors in partnership with medical experts highlights opportunities for peer-to-peer digital storytelling to foster community among survivors and caregivers. FUNDING: Podcast production was supported by the Stanford Comprehensive Cancer Center.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adulto , Humanos , Sobreviventes de Câncer/psicologia , Neoplasias/terapia , Neoplasias/psicologia , Sobreviventes/psicologia , Sobrevivência , Comunicação
2.
J Cancer Surviv ; 18(1): 53-58, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38183579

RESUMO

The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement. Cross-cutting areas of expertise include the following: (a) adolescents and young adults (AYAs), (b) mental health and patient self-management, (c) integration of primary care, and (d) postgraduate medical education. The clinical care model includes embedded survivorship clinics within disease groups in outpatient clinics, novel clinics designed to address unmet needs such as sexual health for women, and primary care-based faculty-led survivorship clinics for patients undergoing active cancer care requiring co-management, those who have completed active therapy and those at high risk for cancer due to genetic risk. Educational initiatives developed to date include an online course and medical textbook for primary care clinicians, a lecture series, monthly research team meetings, and rotations for medical trainees. Patient-facing activities include webinars and a podcast series designed to promote awareness, thus expanding the provision of expert-vetted information. Ongoing research focuses on oncofertility and family building after cancer, improving communication for AYAs, changing mindsets to improve quality of life through targeted digital interventions, increasing capacity to care for cancer survivors, and strengthening collaboration with community partners. IMPLICATIONS FOR CANCER SURVIVORS: Stanford's Cancer Survivorship Program includes a robust transdisciplinary and interdisciplinary research, training and clinical platform that is committed to advancing access and improving care for people living with and beyond cancer, through innovation in design and care delivery.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto Jovem , Humanos , Feminino , Qualidade de Vida/psicologia , Atenção à Saúde , Sobrevivência , Cuidadores , Neoplasias/terapia
3.
Pediatr Blood Cancer ; 71(2): e30798, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38053230

RESUMO

BACKGROUND: Individual- and population-level socioeconomic disadvantages contribute to unequal outcomes among childhood cancer survivors. Reducing health disparities requires understanding experiences of survivors from historically marginalized communities, including those with non-English language preference. PROCEDURE: We partnered with a community-based organization (CBO) serving families of children with cancer in a rural region in California with low socioeconomic status and majority Hispanic/Latino (H/L) residents. We interviewed English- and Spanish-speaking adolescent/young adult (AYA) childhood cancer survivors (≥15 years old, ≥5 years from diagnosis), parents, and CBO staff to evaluate post-treatment needs and impact of CBO support. Data were analyzed qualitatively using applied thematic analysis. Themes were refined through team discussions with our community partners. RESULTS: Twelve AYAs (11 H/L, 11 bilingual), 11 parents (eight H/L, seven non-English preferred), and seven CBO staff (five H/L, five bilingual) participated. AYAs (five female, seven male) were of median (min-max) age 20 (16-32) and 9 (5-19) years post diagnosis; parents (nine female, two male) were age 48 (40-60) and 14 (6-23) years post child's diagnosis. Themes included challenges navigating healthcare, communication barriers among the parent-AYA-clinician triad, and lasting effects of childhood cancer on family dynamics and mental health. Subthemes illustrated that language and rurality may contribute to health disparities. CBO support impacted families by serving as a safety-net, fostering community, and facilitating H/L families' communication. CONCLUSIONS: Childhood cancer has long-lasting effects on families, and those with non-English language preference face additional burdens. Community-based support buffers some of the negative effects of childhood cancer and may reduce disparities.


Assuntos
Desigualdades de Saúde , Neoplasias , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Família/psicologia , Hispânico ou Latino/psicologia , Neoplasias/terapia , Pais/psicologia , Pesquisa Qualitativa , Populações Vulneráveis , Fatores Socioeconômicos , Sobreviventes de Câncer
4.
J Cancer Surviv ; 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37792162

RESUMO

PURPOSE: Adherence to survivorship care is suboptimal among pediatric and adolescent/young adult (AYA) cancer survivors. We evaluated predictors of cancer center-based follow-up among pediatric/AYA cancer survivors, with an emphasis on social determinants of health (SDOH). METHODS: This retrospective cohort study used electronic health record data at an academic medical center to identify patients aged 0-29 years at last cancer treatment who completed treatment 2010-2019. Cancer center-based follow-up was defined by oncology or survivorship clinic visits through 12/31/2022. Multivariate logistic regression models (overall, ages 0-19 [pediatric], 20-29 [YA]) evaluated the association of demographics, clinical/treatment characteristics, and SDOH (insurance type, distance to cancer center, area deprivation index) with clinic attendance. Further modeling accounted for the service area of a community-based organization (CBO) that supports families of children with cancer. RESULTS: A total of 2210 survivors were included (56% pediatric, 44% YA; 66% non-White). Cancer center-based follow-up decreased from 94% 1-year post-treatment to 35% at > 5-7 years. In adjusted analysis, AYAs had the lowest follow-up (5-7 years post-treatment: OR 0.25 [0.15-0.41] for age 25-29; OR 0.25 [0.16-0.41] for age 20-24; OR 0.32 [0.20-0.52] for age 15-19). Survivors residing within the CBO service area were twice as likely to follow-up (OR 2.10 [1.34-3.29]). CONCLUSIONS: Among a diverse population, AYA survivors were vulnerable to loss to follow-up. Other SDOH were not consistently associated with follow-up. Support from a CBO may partly explain these findings. IMPLICATIONS FOR CANCER SURVIVORS: CBOs may strengthen survivorship follow-up within medically underserved communities. More research is needed to understand community support in survivorship.

6.
J Adolesc Young Adult Oncol ; 12(6): 918-922, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37615593

RESUMO

Childhood cancer survivors are recommended to have lifelong survivorship care, yet many become disengaged during pediatric to adult care transitions. We implemented a pilot clinic for adult survivors of pediatric or adolescent and young adult (AYA) leukemia transitioning to adult-focused survivorship care. The clinic featured AYA-specific care, bidirectional communication with primary care, and a quality improvement (QI) cycle. During the 1-year QI period, 27 patients were seen and 21 completed postvisit interviews. The clinic was positively received by patients and primary care providers, showed promise for improving self-management and care coordination, and highlighted the need for novel approaches to connect survivors with primary care.


Assuntos
Sobreviventes de Câncer , Neoplasias , Transição para Assistência do Adulto , Adolescente , Adulto Jovem , Humanos , Criança , Neoplasias/terapia , Sobreviventes , Sobrevivência
7.
JAMA Oncol ; 9(10): 1337-1338, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471071

RESUMO

This essay describes a woman who had received chest irradiation for childhood cancer and the considerations for and against breast cancer risk­reducing mastectomy.

8.
Cancer ; 129(19): 2941-2943, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37489767
9.
JCO Oncol Pract ; 19(5): e650-e659, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36800566

RESUMO

PURPOSE: Childhood cancer survivors report self-monitoring for and worrying about symptoms of disease recurrence and secondary cancers, although symptom-related worry is associated with poorer health-related quality of life. This survey captured pediatric oncologists' beliefs and communication practices regarding symptom self-monitoring for childhood cancer survivors. METHODS: Using a closed-loop snowball sampling technique, pediatric oncologists completed an online survey regarding the importance of symptom self-monitoring for off-therapy patients, the degree to which symptom self-monitoring was perceived to cause stress and worry, and communication practices. RESULTS: 196 pediatric oncologists (White [78%]; female [64%]; Mage = 47 years) from every continent except Antarctica participated. Oncologists believed it is important for off-therapy patients to self-monitor for symptoms of cancer recurrence (90%) and treatment late effects (94%), although some noted that recurrence (30%) and late effects (55%) are typically detected by routine surveillance before symptoms appear. Oncologists varied in their beliefs that off-therapy patients do (31%) or do not (31%) worry unnecessarily about symptoms of recurrence. Two thirds (62%) of oncologists reported often/always discussing with off-therapy patients which symptoms could indicate cancer recurrence, whereas fewer than half (43%) often/always discussed which symptoms were unlikely to indicate recurrence. Oncologists identified a need for education regarding how to communicate around symptom self-monitoring and the potential utility of a screening tool to identify those who worry excessively. CONCLUSION: Despite nearly universal belief that their off-therapy patients should self-monitor for symptoms of disease recurrence and late effects, a substantial proportion of pediatric oncologists do not counsel patients on symptom self-monitoring. Since nearly one-third believe that off-therapy patients worry unnecessarily about symptoms of recurrence, improving patient education regarding which symptoms are and are not medically concerning could decrease stress and improve health-related quality of life for pediatric cancer survivors.


Assuntos
Sobreviventes de Câncer , Neoplasias , Oncologistas , Humanos , Feminino , Criança , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Qualidade de Vida , Oncologia/métodos , Comunicação
10.
J Cancer Educ ; 38(4): 1140-1148, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36456891

RESUMO

This study investigates the resources used by childhood cancer survivors (CCS) to learn about their cancer histories and evaluates if CCS feel these resources prepare them to manage their health needs as young adults. Young adult participants (aged 18-30 years) were diagnosed with cancer at ≤ 10 years and recruited by word of mouth and from social media and/or non-profit organizations and completed semi-structured interviews. A descriptive thematic analysis guided by an essentialist/realist paradigm combined inductive and deductive approaches to identify key themes. Fourteen participants were interviewed, and six key themes were identified: (1) CCS are aware of general cancer history (age at diagnosis, treating hospital, cancer type), (2) CCS are unaware of treatment regimen (medications and duration), (3) CCS want to learn more about their treatment regimens and (4) potential late effects of treatment, (5) CCS use diverse resources to learn about their cancer histories and potential late effects, and (6) survivors' interests to learn about their cancer histories change over time. Limited knowledge of their cancer treatments leaves some CCS unprepared to manage their health needs as young adults or to address potential risk of late effects. CCS recognize their limited knowledge, but the resources available to them fall short of their information needs. Identifying the shortcomings of resources used by CCS provides evidence for how resources need to be improved to meet survivors' cancer education needs.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Criança , Adulto Jovem , Neoplasias/terapia , Sobreviventes
11.
Front Oncol ; 12: 1033993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523979

RESUMO

Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.

12.
Bone Marrow Transplant ; 57(7): 1150-1163, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35523848

RESUMO

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Medula Óssea , Progressão da Doença , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Qualidade de Vida , Transplantados
13.
Acad Pediatr ; 22(8): 1375-1383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35318159

RESUMO

OBJECTIVE: The COVID-19 pandemic prompted health systems to rapidly adopt telehealth for clinical care. We examined the impact of demography, subspecialty characteristics, and broadband availability on the utilization of telehealth in pediatric populations before and after the early period of the COVID-19 pandemic. METHODS: Outpatients scheduled for subspecialty visits at sites affiliated with a single quaternary academic medical center between March-June 2019 and March-June 2020 were included. The contribution of demographic, socioeconomic, and broadband availability to visit completion and telehealth utilization were examined in multivariable regression analyses. RESULTS: Among visits scheduled in 2020 compared to 2019, in-person visits fell from 23,318 to 11,209, while telehealth visits increased from 150 to 7,675. Visits among established patients fell by 15% and new patients by 36% (P < .0001). Multivariable analysis revealed that completed visits were reduced for Hispanic patients and those with reduced broadband; high income, private non-HMO insurance, and those requesting an interpreter were more likely to complete visits. Those with visits scheduled in 2020, established patients, those with reduced broadband, and patients older than 1 year were more likely to complete TH appointments. Cardiology, oncology, and pulmonology patients were less likely to complete scheduled TH appointments. CONCLUSIONS: Following COVID-19 onset, outpatient pediatric subspecialty visits shifted rapidly to telehealth. However, the impact of this shift on social disparities in outpatient utilization was mixed with variation among subspecialties. A growing reliance on telehealth will necessitate insights from other healthcare settings serving populations of diverse social and technological character.


Assuntos
COVID-19 , Telemedicina , Humanos , Criança , Pandemias , Pacientes Ambulatoriais , Agendamento de Consultas
14.
J Cancer Surviv ; 16(1): 24-32, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35107793

RESUMO

PURPOSE: To evaluate the outcomes of an online cancer survivorship course designed to influence practice change in primary care clinicians through asynchronous education that incorporates emotionally sensitive patient stories and practical resources to prepare clinicians to care for cancer survivors. METHODS: The Health After Cancer: Cancer Survivorship for Primary Care continuing medical education (CME) course launched in April 2020. Learners who earned CME credit for the course (n=288) completed a survey that assessed satisfaction, engagement, and intent to change practice. A follow-up survey was completed by a subset of learners (n=47) and evaluated impact on clinical practice. Metrics representing learners' interaction with the course were collected automatically. Quantitative survey data and learner metrics were analyzed descriptively, and qualitative survey data were coded to generate latent themes relevant to learning outcomes. RESULTS: The course reached a global audience of learners from the USA and 40 countries. Each patient case had slight drop-offs in viewership over video play time. Learners reported high satisfaction and relevance to practice. Three latent themes were generated from the qualitative data: improve patient communication, utilize course materials, enhance collaboration with multidisciplinary team. CONCLUSIONS: The course achieved its purpose of educating learners through an asynchronous format that showcased the value of using patient-centered stories to close a knowledge gap related to cancer survivorship care. Learners self-reported changes in practice; however, further assessment needs to be conducted to measure long-term impact to clinical practice. IMPLICATIONS FOR CANCER SURVIVORS: Educational approaches that prepare generalists and specialists to care for cancer survivors are essential to optimize health outcomes for cancer survivors. Ongoing efforts are needed to increase use of these resources throughout medical training and within the primary care community.


Assuntos
Sobreviventes de Câncer , Educação a Distância , Neoplasias , Educação Médica Continuada , Humanos , Neoplasias/terapia , Atenção Primária à Saúde , Sobrevivência
15.
Transplant Cell Ther ; 28(6): 335.e1-335.e17, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34757220

RESUMO

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GVHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. These effects may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Here we provide a systematic review of male-specific late effects in a collaboration among transplantation physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. We used a systematic review methodology to summarize incidence, risk factors, screening, prevention, and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Most of the evidence regarding male GVHD is still based on limited data, precluding strong therapeutic recommendations. Therefore, we recommend systematic screening for male genital GVHD regularly and reporting of cases to large registries to allow for a better understanding. Future research also should address treatment, given the little published evidence currently available. Male-specific endocrine consequences of HCT include hypogonadism, which also may affect bone health. Given the scanty evidence, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases, and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, warranting the offer of sperm preservation for all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, underscoring the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent in HCT recipients compared with the general population; however, subsequent malignancies in general seem to be more prevalent in males than in females, and special attention should be given to skin and oral mucosa. Male-specific late effects, which likely are more underreported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplantation physicians and specialists from other involved disciplines. Future research should be directed toward better data collection on male-specific late effects and on studies about the interrelationships among these late effects, to allow the development of evidence-based effective management practices.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hipogonadismo , Infertilidade , Neoplasias Testiculares , Adulto , Medula Óssea , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hipogonadismo/epidemiologia , Infertilidade/etiologia , Masculino , Qualidade de Vida , Neoplasias Testiculares/etiologia
16.
Pediatr Hematol Oncol ; 39(5): 453-467, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34918996

RESUMO

Chronic myeloid leukemia (CML) is effectively treated with long-term tyrosine kinase inhibitor (TKI) therapy, yet little is known about risks of prolonged TKI exposure in young patients, and long-term effect monitoring is not standardized. We surveyed North American pediatric oncologists (n = 119) to evaluate perceived risk of and surveillance practices for potential toxicities associated with prolonged TKI exposure in children and adolescents/young adults (AYAs) with CML. Survey domains included general and specific risk perceptions and surveillance practices for asymptomatic patients on chronic TKI therapy. We analyzed data descriptively and explored relationships between risk perceptions and surveillance. Risk perceptions varied among oncologists but were similar across six categories (thyroid, cardiac, vascular, metabolic, fertility, psychologic), with less than one-third rating each risk as moderate or high in pediatric and AYA patients. More oncologists perceived moderate or high risk of growth abnormalities in children (62% pediatric, 14% AYA) and financial toxicity in all patients (60% pediatric, 64% AYA). A greater proportion of oncologists with moderate or high perceived risk of thyroid abnormalities reported testing thyroid function compared to those with lower perceived risk; patterns for metabolic risk/lipid tests and cardiac risk/tests were similar. In summary, we found that pediatric oncologists had variable risk perceptions and surveillance practices for potential toxicities associated with prolonged TKI exposure. Standardizing surveillance would help quantify risks and refine recommendations.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2017085 .


Assuntos
Doença Enxerto-Hospedeiro , Leucemia Mielogênica Crônica BCR-ABL Positiva , Médicos , Adolescente , Criança , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adulto Jovem
17.
Cancers (Basel) ; 13(24)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34944883

RESUMO

Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.

18.
J Neurooncol ; 153(2): 225-237, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963961

RESUMO

PURPOSE: Tumor infiltration by immunosuppressive myeloid cells or tumor-associated macrophages (TAMs) contributes to tumor progression and metastasis. In contrast to their adult counterparts, higher TAM signatures do not correlate with aggressive tumor behavior in pediatric brain tumors. While prominent TAM infiltrates exist before and after radiation, the degree to which irradiated macrophages and microglia support progression or leptomeningeal metastasis remains unclear. Patients with medulloblastoma often present with distant metastases and tumor recurrence is largely incurable, making them prime candidates for the study of novel approaches to prevent neuroaxis dissemination and recurrence. METHODS: Macrophage depletion was achieved using CSF-1 receptor inhibitors (CSF-1Ri), BLZ945 and AFS98, with or without whole brain radiation in a variety of medulloblastoma models, including patient-derived xenografts bearing Group 3 medulloblastoma and a transgenic Sonic Hedgehog (Ptch1+/-, Trp53-/-) medulloblastoma model. RESULTS: Effective reduction of microglia, TAM, and spinal cord macrophage with CSF-1Ri resulted in negligible effects on the rate of local and spinal recurrences or survival following radiation. Results were comparable between medulloblastoma subgroups. While notably few tumor-infiltrating lymphocytes (TILs) were detected, average numbers of CD3+ TILs and FoxP3+ Tregs did not differ between groups following treatment and tumor aggressiveness by Ki67 proliferation index was unaltered. CONCLUSION: In the absence of other microenvironmental influences, medulloblastoma-educated macrophages do not operate as tumor-supportive cells or promote leptomeningeal recurrence in these models. Our data add to a growing body of literature describing a distinct immunophenotype amid the medulloblastoma microenvironment and highlight the importance of appropriate pediatric modeling prior to clinical translation.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Transdução de Sinais , Criança , Proteínas Hedgehog , Humanos , Fator Estimulador de Colônias de Macrófagos , Macrófagos , Receptores Proteína Tirosina Quinases , Receptor de Fator Estimulador de Colônias de Macrófagos , Microambiente Tumoral
19.
BMC Cancer ; 21(1): 474, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926411

RESUMO

BACKGROUND: Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. METHODS: We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), electrocardiogram (EKG), thyroid stimulating hormone (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. RESULTS: 66 patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), EKG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), EKG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, respectively, 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. CONCLUSIONS: Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Vigilância da População/métodos , Inibidores de Proteínas Quinases/efeitos adversos , Absorciometria de Fóton/estatística & dados numéricos , Adolescente , Determinação da Idade pelo Esqueleto/estatística & dados numéricos , Sobreviventes de Câncer , Criança , Dasatinibe/efeitos adversos , Dasatinibe/uso terapêutico , Ecocardiografia/estatística & dados numéricos , Eletrocardiografia/estatística & dados numéricos , Feminino , Proteínas de Fusão bcr-abl , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Terapia de Alvo Molecular/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Tireotropina/análise
20.
J Mech Behav Biomed Mater ; 119: 104454, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826987

RESUMO

Mechanically-assisted crevice corrosion (MACC) is a phenomenon known to cause complications in modular orthopedic implants, particularly at metal-metal taper junctions. Previous studies of the properties and corrosion performance of an interfacial polymeric self-reinforced composite (SRC) gaskets have shown its capability as a high-strength, insulating barrier against oxide abrasion and metal degradation of metal-metal (or metal-hard) contacts in MACC conditions. This study characterizes the short-term tribocorrosion performance of poly (ether ether ketone) SRCs (SRC-PEEK) and polyethylene SRC (SRC-PE) films under in vitro test conditions for head-neck modular junction designs in hip replacement devices. SRC films composed of SRC-PEEK and SRC-PE were seated between 9/10 femoral head bores and stem tapers as thin interfacial gaskets and tested against metal-metal controls under short-term cyclic loading conditions in a custom in vitro test setup. Head-neck seating mechanics were measured, followed by incremental cyclic fretting corrosion testing with monitoring of fretting current, force, and relative micromotion between head and neck components during cyclic loading. SRC-PEEK tapers had a seating subsidence that was approximately three times that of the SRC-PE tapers and nine times that of controls. SRC-PE tapers, likely due to low friction, partially failed to lock during seating resulting in a pushing up of the head on the taper. Average fretting currents were significantly lower for both SRC groups (less than 0.3 µA at 4000 N) compared to control tapers experiencing fretting corrosion currents between 1.7 µA and 32 µA, (p < 0.05). SRC-PEEK gaskets exhibited similar subsidence and micromotion performance as controls while SRC-PE tapers experienced over 240 µm of subsidence during seating and loading conditions. The SRC-PE low-friction properties likely caused insufficient taper locking, which may increase the risk of improper head seating or head disassociation. These results show that SRC-PEEK gaskets, unlike SRC-PE gaskets, can maintain adequate frictional locking at the taper junction and prevent the onset of MACC. SRC-PEEK gaskets improve the performance of modular taper junctions and could be considered as a potential solution to mitigate fretting corrosion.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Corrosão , Éter , Humanos , Cetonas , Polietileno , Desenho de Prótese , Falha de Prótese
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