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  • 1
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 110, No. 6 ( 2023-05-16), p. 685-700
    Abstract: The Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation. Methods This was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model. Results In the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach’s α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever). Conclusion This study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2006309-X
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  • 2
    In: Developmental Cognitive Neuroscience, Elsevier BV, Vol. 66 ( 2024-04), p. 101375-
    Type of Medium: Online Resource
    ISSN: 1878-9293
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2572271-2
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3526-3526
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3526-3526
    Abstract: Introduction: Penile carcinoma is a rare malignancy accounting for 1% of cancers in men in the U.S. Although the overall 5-year survival rate is 83% for those with localized disease, this survival rate is reduced to 48% for those with regional lymph node involvement. Thus, there is an unmet need to identify prognostic factors for those at high risk of poor outcomes. Methods: Demographic and clinical information was obtained from electronic medical records among 230 men diagnosed with penile carcinoma between 1986 and 2013. The log-rank test was used to test for differences in overall survival (censored at 12, 36, and 60 months) by demographic and clinical variables. Overall survival was defined as date of cancer diagnosis to date of event or date of last follow-up. Modeling building approaches were utilized to identify the most informative variables associated with overall survival including backward elimination analysis and classification and regression tree (CART) analysis. Results: Following univariable analyses, a full multivariable model was generated and reduced to the most informative covariates using backward elimination analysis. The reduced model revealed penile tumors located on the penis glans (HR =0.48, 95% CI=0.27-0.85) or NOS (HR=0.45, 95% CI=0.25-0.84) and undetermined tumor differentiation (HR=0.48, 95% CI=0.27-0.86) was associated with a reduced risk of dying and late stage disease (III/IV) was associated with an increased risk of death (HR=2.83, 95% CI=1.68-4.75). To identify potential novel prognostic factors, the full model was subjected to CART analysis which identified four subgroups based on three covariates: tumor stage, tumor site, and marital status. Compared to risk-group 1 (Stage 0-II and penis glans/NOS), men in risk-group 3 (Stage 0-II, prepuce/penis corpus/overlapping lesion, single/widowed/divorced) exhibited a 4.9-fold increased risk of death (HR =4.87; 95% CI 2.28-10.42) and men in risk-group 4 (Stages III/IV) had a slightly attenuated increased risk of death (HR =4.62; 95% CI 2.68-7.98). When CART risk-groups were included into a single model and adjusted for alcohol use, ethnicity, and tumor differentiation, the point estimates were slightly somewhat attenuated but the overall trend was the same. Conclusion: This analysis of a cohort of patients diagnosed with penile cancer identified prognostic models with the most informative covariates significantly associated with overall survival. Using a decision tree approach, we identified four novel patient risk subgroups that demonstrated early stage patients who were not married had significantly worse 5-year survival (18.2%) compared to late stage patients (38.2%). These data may suggest that social support network has a beneficial impact on patient outcomes even among late stage patients. Citation Format: Monica E. Reyes, Heloise Borges, Muhamed S. Adjao, Nisha Vijayakumar, Philippe E. Spiess, Matthew B. Schabath. A novel prognostic model demonstrates social support has a beneficial impact on penile carcinoma outcomes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3526.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    SAGE Publications ; 2020
    In:  Cancer Control Vol. 27, No. 1 ( 2020-01-01), p. 107327482092472-
    In: Cancer Control, SAGE Publications, Vol. 27, No. 1 ( 2020-01-01), p. 107327482092472-
    Abstract: Although penile carcinoma is a rare malignancy, there is still an unmet need to identify prognostic factors associated with poor survival. In this study, we utilized demographic and clinical information to identify the most informative variables associated with overall survival in patients with penile cancer. From a full model including all covariates found to be statistically significant in univariable analyses, we identified a parsimonious reduced model containing tumor site (penis glans: hazard ratio [HR] = 0.48; 95% CI: 0.28-0.85 and penis not otherwise specified: HR = 0.45; 95% CI: 0.25-0.84), undetermined tumor differentiation (HR = 0.48; 95% CI: 0.27-0.86), and TNM stage III/IV (HR = 2.83; 95% CI: 1.68-4.75). When all of the covariates from the full model were subjected to classification and regression tree analysis, we identified 6 novel risk groups. Of particular interest, we found marriage was associated with substantial improvement in survival among men with the same stage and disease site. Specifically, among single/widowed/divorced men with TNM stage 0-II and prepuce/penis corpus/overlapping lesions had worse survival (5-year survival = 18.2%) versus married men (5-year survival = 62.5%). Since marital status is linked to social support, these findings warrant a deeper investigation into the relationships between disease prognosis and social support in patients with penile carcinoma.
    Type of Medium: Online Resource
    ISSN: 1073-2748 , 1073-2748
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2004182-2
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  • 5
    In: Journal of Pediatric Surgery, Elsevier BV, Vol. 56, No. 4 ( 2021-04), p. 641-647
    Type of Medium: Online Resource
    ISSN: 0022-3468
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2039299-0
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 990-990
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 990-990
    Abstract: Distinct racial disparities are evident in CRC prognosis with Black patients experiencing worse outcomes than Hispanics and Whites. In a prior study of Health Related Quality of Life (HR-QoL) in a cohort of CRC patients, we observed that racial minority patients experienced lower HR-QoL scores compared to White CRC patients. Therefore, in this study, we focused on the identification of patterns of racial disparities in HR-QoL scores and relationship to differences in prognosis. White (N=450), Hispanic (N=366), and Black (N=316) CRC patients within 1 year of diagnosis at MD Anderson Cancer Center completed the SF-12 quality of life questionnaire to determine Mental Composite Summary (MCS) and Physical Composite Summary (PCS) scores. Participants also completed a questionnaire to collect epidemiology and sociodemographic variables. Vital status and histology information was obtained from the institutional tumor registry. Racial disparities were reported in HR-QoL with both Black and Hispanic patients reporting lower mean PCS and MCS scores compared to White patients, suggesting poorer HR-QoL in these populations. We observed differences in patterns of association between epidemiology and sociodemographic variables and poor HR-QoL by race. Hispanics who never married were at higher risk of poor physical HR-QoL (OR: 2.55(1.15-5.67), P=0.021) compared to married patients, which was not observed for White or Black CRC patients. Similarly, CRC patients with some college education was associated with a decreased risk of poor PCS, but only in Hispanics (OR: 0.26(0.13-0.52), P & lt;0.0001). White females have about two-fold risk of poor PCS (P=2.00 x 10-4) and MCS (P=2.21 x 10-4) scores compared to White males. This relationship was also observed for Black females OR: 2.28(1.35-3.84), but not Hispanic females. Among CRC patients reporting poor PCS ( & lt;50), significant differences in median survival times (MSTs) were observed by race. Hispanic patients had the highest MST at 85.4 months followed by Blacks (47.8 months) and Whites (43.2 months). A similar relationship was observed for poor MCS ( & lt;50) stratified by race with MST times of 81.9 months for Hispanics, 40.8 months for Blacks, and 54.1 months for Whites. In conclusion, we identified patterns of racial disparities in epidemiology and sociodemographic factors that correspond to poor baseline HR-QoL in CRC patients. We also demonstrated that a prognostic correlation exists between baseline HR-QoL and patient overall survival, and that this relationship is influenced by race. The patterns of racial disparity identified in this study can be an important tool for assessing the underlying mediators of HR-QoL in CRC patients and to further identify those who are particularly at risk for poor prognosis. Citation Format: Michelle A. T. Hildebrandt, Alem A. Belachew, Monica E. Reyes, Yuanqing Ye, Xifeng Wu. Patterns of racial disparities in health-related quality of life among colorectal cancer patients and relationship with survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 990. doi:10.1158/1538-7445.AM2017-990
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 25, No. 3 ( 2016-03-01), p. 540-546
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 3 ( 2016-03-01), p. 540-546
    Abstract: Background: The Wnt/β-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high-penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods: We assessed 172 variants in 26 genes from the Wnt/β-catenin pathway in 809 colorectal cancer cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results: Eighteen SNPs in the pathway were significantly associated with colorectal cancer risk (P & lt; 0.05) in the discovery phase. We observed a significant dose-response increase in colorectal cancer risk by number of risk genotypes carried (P = 4.19 × 10−8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for colorectal cancer risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 [95% confidence interval (CI), 0.76–0.94, P = 0.001]. Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis—OR, 1.42; 95% CI, 1.16–1.74; P = 0.00085. Functional assessment identified several potential biologic mechanisms underlying these associations. Conclusions: Our findings suggest that common germline variants in the Wnt/β-catenin pathway may be involved in colorectal cancer development. Impact: These variants may be informative in colorectal cancer risk assessment to identify individuals at increased risk who would be candidates for screening. Cancer Epidemiol Biomarkers Prev; 25(3); 540–6. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 569-569
    Abstract: Background: Inflammatory breast cancer (IBC) is a rare and aggressive type of advanced breast cancer with a poor long-term outcome and a high risk of recurrence. Although one of the most common clinical manifestations of IBC is erythema of the skin overlying the breast, whether inflammation is involved in IBC has not yet been tested by pathologic examination of IBC specimens. Therefore, whether inflammation pathways are involved in the pathogenesis of IBC is still not clear. A large body of evidence indicates that chronic inflammation is a risk factor for cancer. Nonsteroidal anti-inflammatory drugs have been reported to reduce the risk of developing some solid cancers, including breast cancer. Cyclooxygenase (COX)-2 is the inducible isoenzyme catalyzing the conversion of arachidonic acid to prostanoids. COX-2 upregulation has been linked to breast tumorigenesis or inflammatory diseases, and COX-2 overexpression increases the growth rate and invasiveness of breast cancer cells. We tested the hypothesis that the COX-2 pathway is involved in IBC tumor growth and metastasis. Methods and Results: We examined the expression level of COX-2 and the concentrations of its enzymatic products by mass spectrometry (LC/MS/MS). We also determined the effect of inhibition of the COX2 pathway on cell proliferation, migration, invasiveness, and epithelial-mesenchymal transition (EMT) in IBC both in vitro and in vivo. We found that levels of COX-2 and its enzymatic products prostaglandins (PG), such as PGE2 and PGF2α, were higher in IBC than in non-IBC cell lines. Both PGE2 and PGF2α markedly enhanced the migration and invasion of SUM149 IBC cells, suggesting that COX-2 and its metabolites may play an important role in IBC development and progression. We examined the expression levels of COX-2 and EGFR in 25 IBC patient biopsy samples and found that the expression of COX-2 was positively correlated with the levels of EGFR in these tissues. To illustrate how COX-2 and EGFR are regulated in IBC cells, we treated SUM149 cells with EGF. We found that EGF stimulation increased COX-2 levels. COX-2 expression was notably downregulated in EGFR shRNA stably transfected SUM149 cells, suggesting that the upregulation of COX-2 is mediated through EGFR signaling. Furthermore, a selective COX-2 inhibitor, celecoxib, dramatically inhibited IBC tumor growth in a SUM149 IBC xenograft model. These celecoxib-treated tumors exhibited high expression of the epithelial marker E-cadherin and low expression of the mesenchymal marker vimentin compared with untreated tumors, suggesting that celecoxib inhibits epithelial-mesenchymal transition. Conclusions: Our results suggest that inflammatory mediators indeed play an important role in IBC cells. Targeting inflammatory pathways may represent an effective therapeutic approach to suppress tumorigenicity and prevent metastasis in IBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 569. doi:1538-7445.AM2012-569
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  JCO Oncology Practice Vol. 16, No. 10 ( 2020-10), p. e1192-e1201
    In: JCO Oncology Practice, American Society of Clinical Oncology (ASCO), Vol. 16, No. 10 ( 2020-10), p. e1192-e1201
    Abstract: Biobanks usually do not collect transgender and gender-diverse (TGD) demographic information, hindering research on cancer risk and biological effects related to gender-affirming interventions. METHODS: In August 2019, 172 scientists involved in biobanking research at a single institution (H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL) were invited to complete a survey measuring knowledge and attitudes about TGD health and research practices. Quantitative and qualitative analyses were performed. RESULTS: Among 47 respondents, there was high agreement (77%) regarding the importance of collecting TGD identities and histories of gender-affirming treatments with biospecimens, which was contrasted by low self-reported rates of respondents’ biorepositories allowing for the entry of TGD identities (14.9%) and histories of gender-affirming interventions (8.5%). There was high interest in receiving education regarding the unique cancer health needs of TGD patients (74%), and knowledge questions yielded high percentages of “neutral” and “don’t know or prefer not to answer” responses. After completing the survey, confidence in knowledge of health needs for TGD patients decreased significantly (48.9% were confident during the presurvey assessment v 36.2% in the postsurvey assessment; P 〈 .001). Qualitative analysis of open-ended questions indicated overall support of TGD data inclusion in biobanks along with perceived barriers to inclusion of such data in biobanks. CONCLUSION: To our knowledge, this was the first study of researchers to assess knowledge, attitudes, and research practices regarding TGD patients. Overall, there was limited knowledge about TGD health and cancer needs and low rates of TGD demographic data collection but a high interest in receiving education regarding this community.
    Type of Medium: Online Resource
    ISSN: 2688-1527 , 2688-1535
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 3005549-0
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  • 10
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. Suppl_1 ( 2019-08-02)
    Abstract: Impaired mitochondrial function has been implicated as a mechanism of doxorubicin-induced cardiotoxicity, however the precise genes that regulate this process in human cardiomyocytes remain to be elucidated. We hypothesized that doxorubicin significantly alters expression of genes involved in mitochondrial function in human cardiomyocytes, which in turn impairs mitochondrial respiration. Towards this, we treated human inducible pluripotent stem cell (iPSC)-cardiomyocytes with doxorubicin at 15 different time and dose conditions. Gene expression was assessed by RNAseq for each condition and 169 genes involved in mitochondrial function were analyzed for differential expression between control and treated conditions. Mitochondrial respiration (basal respiration, ATP production, maximal respiration, and spare respiratory capacity) was measured using the Seahorse Bioscience XFe96 Cell Mito Stress Test kit and correlated to gene expression levels. Of the 169 genes analyzed, 25 were significantly differentially expressed (P 〈 0.05) including GPX4 (P = 5.70 x 10 -3 ). Expression of GPX4 remained significant in pairwise comparisons by dose for day 2 and qRT-PCR validation confirmed a dose-dependent decrease in GPX4 expression. Maximal respiration (r = -0.62; P = 0.031) and spare respiratory capacity (r = -0.67; P = 0.017) correlated with GPX4 expression in doxorubicin-treated iPSC-cardiomyocytes. GPX4 encodes a glutathione peroxidase that is responsible for protecting the cell against oxidative damage. Damage due to reactive oxygen species (ROS) is one of the established mechanisms of anthracycline-induced cardiac damage. Our findings underscore a role for mitochondrial function and ROS in the development of doxorubicin-induced cardiotoxicity and implicates GPX4 in this process. The assessment of doxorubicin-altered gene expression in iPSC-cardiomyocytes may provide insight into how impaired mitochondrial respiration leads to cardiotoxicity and heart failure in cancer survivors treated with doxorubicin and other anthracyclines.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467838-X
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