Incidence and Risk Factors for De Novo Cutaneous Squamous Cell Carcinoma in a Contemporary Cohort of Long-Term Hematopoietic Cell Transplantation Survivors.
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ABSTRACT:
SUBMITTER: Berano Teh J
PROVIDER: S-EPMC8316257 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Incidence and Risk Factors for De Novo Cutaneous Squamous Cell Carcinoma in a Contemporary Cohort of Long-Term Hematopoietic Cell Transplantation Survivors.
Berano Teh Jennifer J Abdulla Farah F Peng Kelly K Atencio Liezl L Echevarria Meagan M Iukuridze Aleksi A Geller Alan C AC Wong F Lennie FL Forman Stephen J SJ Nakamura Ryotaro R Modi Badri B Armenian Saro H SH
The Journal of investigative dermatology 20210218 8
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Project description:BackgroundThere is a paucity of studies describing the incidence and risk factors for late-occurring (≥1 year) infectious complications in contemporary survivors of hematopoietic cell transplantation (HCT).MethodsThis was a retrospective cohort study of 641 1-year survivors of HCT, transplanted between 2010 and 2013 as adults, and in remission from their primary disease. Standardized definitions were used to characterize viral, fungal, and bacterial infections. Cumulative incidence of infections was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained, adjusted for relevant covariates.ResultsMedian age at HCT was 55.2 years (range 18.1-78.1 years); 54.0% were survivors of allogeneic HCT. The 5-year cumulative incidence of a late-occurring infection for the entire cohort was 31.6%; the incidence of polymicrobial (≥2) infections was 10.1%. In survivors who developed at least one infection, the 5-year incidence of a subsequent infection was 45.3%. Among allogeneic HCT survivors, patients with acute lymphoblastic (HR = 1.82 95% CI [1.12-2.96]) or myeloid (HR = 1.50 95% CI [1.02-2.20]) leukemia, and those with an elevated HCT-Comorbidity index score (HR = 1.09 95% CI [1.01-1.17]) were more likely to develop late-occurring infections; there was an incremental risk associated with severity of graft versus host disease (GVHD) at 1-year post-HCT (mild: HR = 2.17, 95% CI [1.09-4.33]; moderate/severe: HR = 3.78, 95% CI [1.90-7.53]; reference: no GVHD).ConclusionsThe burden of late-occurring infections in HCT survivors is substantial, and there are important patient- and HCT-related modifiers of risk over time. These findings may help guide personalized screening and prevention strategies to improve outcomes after HCT.
| S-EPMC8086032 | biostudies-literature
Project description:BackgroundLittle is known about whether UVB can directly influence epigenetic regulatory pathways to induce cutaneous squamous cell carcinoma (CSCC). This study aimed to identify epigenetic-regulated signalling pathways through global methylation and gene expression profiling and to elucidate their function in CSCC development.MethodsGlobal DNA methylation profiling by reduced representation bisulfite sequencing (RRBS) and genome-wide gene expression analysis by RNA sequencing (RNA-seq) in eight pairs of matched CSCC and adjacent normal skin tissues were used to investigate the potential candidate gene(s). Clinical samples, animal models, cell lines, and UVB irradiation were applied to validate the mechanism and function of the genes of interest.FindingsWe identified the downregulation of the TGF-β/BMP-SMAD-ID4 signalling pathway in CSCC and increased methylation of inhibitor of DNA binding/differentiation 4 (ID4). In normal human and mouse skin tissues and cutaneous cell lines, UVB exposure induced ID4 DNA methylation, upregulated DNMT1 and downregulated ten-eleven translocation (TETs). Similarly, we detected the upregulation of DNMT1 and downregulation of TETs accompanying ID4 DNA methylation in CSCC tissues. Silencing of DNMT1 and overexpression of TET1 and TET2 in A431 and Colo16 cells led to increased ID4 expression. Finally, we showed that overexpression of ID4 reduced cell proliferation, migration, and invasion, and increased apoptosis in CSCC cell lines and reduced tumourigenesis in mouse models.InterpretationThe results indicate that ID4 is downregulated by UVB irradiation via DNA methylation. ID4 acts as a tumour suppressor gene in CSCC development.FundingCAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-3-021, 2017-I2M-1-017), the Natural Science Foundation of Jiangsu Province (BK20191136), and the Fundamental Research Funds for the Central Universities (3332019104).
| S-EPMC7317242 | biostudies-literature
Project description:Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.
| S-EPMC11012944 | biostudies-literature
Project description:Cardiovascular disease (CVD) is a leading cause of late morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. HCT-specific CVD risk prediction models are needed to facilitate early screening and prevention. In the current study, patients who underwent HCT at City of Hope (COH) and survived 1-year free of clinically evident CVD (N = 1828) were observed for the development of heart failure (HF) or coronary artery disease (CAD) by 10-years from index date (1 year from HCT). CVD occurred in 135 individuals (92 HF, 43 CAD). Risk prediction models were developed for overall CVD (HF and/or CAD) using COH-derived integer risk scores. Risk scores based on selected variables (age, anthracycline dose, chest radiation, hypertension, diabetes, smoking) achieved an area under the curve (AUC) and concordance (C) statistic of 0.74 and 0.72 for CVD; these varied from 0.70 to 0.82 according to CVD subtype (HF or CAD). A Fred Hutchinson Cancer Research Center case cohort (N = 580) was used to validate the COH models. Validation cohort AUCs ranged from 0.66 to 0.75. Risk scores were collapsed to form statistically distinct low-, intermediate-, and high-risk groups, corresponding to 10-year cumulative incidences of CVD of 3.7%, 9.9%, and 26.2%, respectively. Individuals in the high- and intermediate-risk groups were at 7.8-fold (95% confidence interval, 5.0-12.2) and 2.9-fold (95% confidence interval, 1.9-4.6) risk of developing CVD (referent group: low risk). These validated models provide a framework on which to modify current screening recommendations and for the development of targeted interventions to reduce the risk of CVD after HCT.
| S-EPMC6058239 | biostudies-literature
Project description:Positive thoughts and emotions contribute to overall psychological health in diverse medical populations, including patients undergoing HSCT. However, few studies have described positive psychological well-being (eg, optimism, gratitude, flourishing) in patients undergoing HSCT using well-established, validated patient-reported outcome measures. We conducted cross-sectional secondary analyses of baseline data in 156 patients at 100 days post-HSCT enrolled in a randomized controlled trial of a psychological intervention (ClinicalTrials.gov identifier NCT05147311) and a prospective study assessing medication adherence at a tertiary care academic cancer center from September 2021 to December 2022. We used descriptive statistics to outline participant reports of positive psychological well-being (PPWB) using validated measures for optimism, gratitude, positive affect, life satisfaction, and flourishing. The participants had a mean age of 57.4 ± 13.1 years, and 51% were male (n = 79). Many, but not all, participants reported high levels of PPWB (ie, optimism, gratitude, positive affect, life satisfaction, and flourishing), defined as agreement with items on a given PPWB measure. For example, for optimism, 29% of participants did not agree that "overall, I expect more good things to happen to me than bad." Aside from life satisfaction, mean PPWB scores were higher in the HSCT population than in other illness populations. Although many patients with hematologic malignancies undergoing HSCT report high levels of PPWB, a substantial minority of patients reported low PPWB (i.e., no agreement with items on a given PPWB measure). Because PPWB is associated with important clinical outcomes in medical populations, further research should determine whether an intervention to promote PPWB can improve quality of life in HSCT recipients.
| S-EPMC10529897 | biostudies-literature
Project description:This investigation characterized sexual activity and sexual function in hematopoietic cell transplantation (HCT) survivors, compared them with norms, and examined factors associated with sexual dysfunction, with the goal of identifying targets for intervention to improve sexual health. Surviving adults from a large transplantation center were asked to complete an annual survey with a core of health questions and a module on sexual activity and function. Participants completed the Sexual Function Questionnaire, Cancer and Treatment Distress form, and Revised Dyadic Adjustment Scale. Clinical data were collected from the transplantation medical database. Multivariate logistic regressions identified factors associated with sexual activity and function. Participating survivors (n = 1742) were a mean of 11.9 years (range, .4 to 43.1 years) after HCT, mean age 57.6 years, and 53% male. Women were more likely than men to report being sexually inactive in the past year (39% versus 27%) and, among those sexually active, to report low sexual function (64% versus 32%). Male and female survivors reported lower rates of sexual activity and function than comparison norms (all P < .01). In regressions, factors associated with being sexually inactive included older age, having <4 years of college education, low performance status, and not being in a committed relationship. Additional factors for men included receipt of nonmyeloablative conditioning and not being employed or in school. Low sexual functioning for men and women was associated with low performance status, and, for women, a committed relationship of lower quality, while for men the association was with older age. Sexual dysfunction is common in both men and women after HCT, regardless of time since treatment. Survivors need routine evaluation and access to multimodal interventions.
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Project description:ImportanceCutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential, but epidemiologic data are poor. Changes to the National Cancer Registration and Analysis Service (NCRAS) in England have allowed more accurate data analysis of primary and metastatic cSCC since 2013.ObjectiveTo assess the national incidence of cSCC and metastatic cSCC (mcSCC) in England from 2013 through 2015.Design, setting, and participantsThis national population-based study identified a cohort of patients with cSCC and mcSCC in England from January 1, 2013, through December 31, 2015. Patients were identified using diagnostic codes derived from pathology reports in the NCRAS. Data were analyzed from March 1, 2017, through March 1, 2018.Main outcomes and measuresIncidence rates across sex and risk factors for cSCC were derived from the NCRAS data. Risk of occurrence of mcSCC among the population with cSCC was assessed with Cox proportional hazards regression analysis to determine indicators of mcSCC.ResultsAmong the 76 977 patients with first primary cSCC in 2013 through 2015 (62.7% male; median age, 80 years [interquartile range, 72-86 years]), the age-standardized rates for the first registered cSCC in England from 2013 through 2015 were 77.3 per 100 000 person-years (PY) (95% CI, 76.6-78.0) in male patients and 34.1 per 100 000 PY (95% CI, 33.7-34.5) in female patients. Increased primary cSCC tumor count was observed in older, white male patients in lower deprivation quintiles. After a maximum follow-up of 36 months, cumulative incidence of mcSCC developed in 1.1% of women and 2.4% of men with a primary cSCC. Significant increases in the risk of metastasis with adjusted hazard rates of approximately 2.00 were observed in patients who were aged 80 to 89 years (hazard ratio [HR], 1.23; 95% CI, 1.07-1.43), 90 years or older (HR, 1.35; 95% CI, 1.09-1.66), male (HR, 1.79; 95% CI, 1.52-2.10), immunosuppressed (HR, 1.99; 95% CI, 1.64-2.42), and in higher deprivation quintiles (HR for highest quintile, 1.64; 95% CI, 1.35-2.00). Primary cSCC located on the ear (HR, 1.70; 95% CI, 1.42-2.03) and lip (HR, 1.85; 95% CI, 1.29-2.63) were at highest risk of metastasis.Conclusions and relevanceThis study presents the first national study of the incidence of mcSCC. With limited health care resources and an aging population, accurate epidemiologic data are essential for informing future health care planning, identifying high-risk patients, and evaluating skin cancer prevention policies.
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Project description:Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi's sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients' age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.
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Project description:Hematopoietic stem cell transplantation (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications that may result in chronic illness. Unfortunately, no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), which are designed specifically to provide guidance for making healthy food choices. The primary aim of this study was to evaluate diet quality and nutrient intake adequacy of HCT survivors. A secondary aim was to assess these survivors' willingness to take part in a future dietary intervention. The dietary intake of adults who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1 year post-transplantation was assessed using the Block 2014 food frequency questionnaire, and diet quality was estimated using the Healthy Eating Index 2015. Nutrient intake adequacies of the group were estimated by the estimated average requirement cutpoint method. Survivors' (n = 90) HEI-2015 scores averaged 61.6 ± 1.1. Adherence to a good-quality diet was reported by only 10% of survivors. Intakes of vitamins A, C, and D, as well as magnesium and calcium, suggested inadequacy. Fiber intake at 8.9 g per 1000 kcal/day fell below the recommended adequate intake. "Change in taste" was associated with lower quality of diet (P = .02). HCT survivors within 2 years post-transplantation were more receptive than survivors beyond 2 years to participating in a dietary intervention (95% versus 65%; P = .0013). Adult HCT survivors reported less-than-optimal adherence to the 2015-2020 DGA and had numerous shortfall nutrient intakes; however, their willingness to participate in a dietary intervention was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care.
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Project description:Long-term survival after hematopoietic cell transplantation (HCT) is now an expected outcome. The growing population of survivors is at risk of developing treatment-related complications, including cardiovascular disease (CVD). A nested case-controlled design was used to identify clinical and treatment-related risk factors for development of late (1+ years after HCT) CVD. Cases were identified from a cohort of 1+-year survivors who underwent transplantation at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and duration of follow-up. Sixty-three patients with late CVD were identified, 44 (69.8%) with a coronary artery event and 19 (30.2%) with a cerebrovascular event. Median age at HCT was 49.0 years. Median age at onset of late CVD was 54.0 years; 66.7% of the affected patients had undergone autologous HCT. Multivariate logistic regression analysis showed that the presence of multiple cardiovascular risk factors (2 or more of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT was associated with a 5.2-fold increased risk of late CVD (P < .01), and that pre-HCT chest radiation exposure was associated with a 9.5-fold greater risk of coronary artery disease (P = .03). Pre-HCT exposure to chest radiation and the presence of comorbidities were primarily responsible for the risk associated with late CVD after HCT. These data form the basis for developing predictive models for identifying high-risk individuals for targeted surveillance and aggressive management of comorbidities.
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