Background: Patients with skin of color (P-SOC) are disproportionately burdened by lupus and often have worse disease outcomes than white patients. This is partly because educational materials underrepresent P-SOC, thereby promoting unconscious bias and clinical deficiencies among practitioners. Purpose: We sought to measure providers' confidence in diagnosing the cutaneous manifestations of lupus (i.e., lupus-related rashes) in P-SOC and to assess which factors influenced their confidence. Research Design: We created and distributed a survey that gathered information about participants' personal characteristics, clinical specialty, training, and current practice as well as measuring their confidence assessing lupus-related rashes in various skin tones. Study Sample: Practitioners from the fields of rheumatology, dermatology, and internal medicine in the greater St. Louis area (Missouri, USA) participated in the survey. Analysis: We compared practitioners' mean confidence levels assessing lupus-related rashes in patients with fair skin and P-SOC with a linear mixed effects model and used univariate and multivariate linear regression models to determine if the aforementioned factors correlated with confidence. Results: Participants' mean confidence in diagnosing lupus-related rashes in P-SOC was significantly lower than assessing such findings in patients with fair skin ( p = .009). Several factors correlated with confidence level at a univariate level; however, the multivariate model revealed experience as the only factor significantly associated with confidence ( p = .001). Conclusions: Providers report significantly less confidence assessing lupus-related rashes in P-SOC than in patients with fair skin. Our analysis demonstrates that experience positively correlates with confidence and suggests that interventions which enhance practitioners' exposure to and experience with these rashes in P-SOC can improve clinical confidence as well as patient outcomes.
The current clinicopathologic diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to the different genetic and epigenetic backgrounds not currently incorporated into CRC staging which can ultimately lead to treatment failure. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Recently, we and others have identified “stem-like” molecules with the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N=21) obtained from colectomies and 5 µm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N=8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher (p=0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase (p=0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p<0.0001). These results suggest HURP’s potential as a tumor marker in CRC. In contrast to those results, ZEB1 mRNA expression in tumors did not differ from that observed in normal adjacent tissue; moreover, a tendency of mRNA to a decrease (n.s.) was observed. IHC for ZEB1 showed immunostaining in all analyzed cases. Weak staining was observed in both tumor and stroma (average intensity score = ++, n.s.). Further stratification of patients by race revealed that in Caucasian-American (CA) patients, staining of ZEB1 was less likely to be associated with disease progression or death after at least 2 years of follow-up. Interestingly, samples obtained from African-American (AA) individuals, known to have worse CRC outcomes, had an association between ZEB1 presence and poor survival regardless of the immunostaining intensity. These findings suggest that IHC localization of ZEB1 may represent a marker of a poor CRC prognosis, particularly in AA patients. However, one must be careful not to over-interpret these results as a Fischer’s Exact test revealed a non-significant p value = 0.387. Any conclusions about population-based distribution of poor prognosis with regards to ZEB1 positive CRC will require an adequately powered sample size. Overall, we have identified two stem cell-like molecules, HURP and ZEB1, with potential as markers of aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christian R. Gomez, Christopher Lahr. HURP and ZEB1: Novel prognostic biomarkers in colorectal carcinomas. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B03.
Gout, a common form of inflammatory arthritis, is characterized by deposition of monosodium urate crystals in articular and periarticular tissues. Repeated flares of gout cause joint damage as well as significant healthcare utilization and decreased quality of life. Individuals with chronic kidney disease (CKD) have a higher prevalence of gout. Treating individuals with CKD and gout is challenging due to the lack of quality data to guide management in this specific population. This often leads to suboptimal treatment of patients with gout and impaired renal function, as concerns regarding the efficacy and safety of available gout therapies in this population often result in significant inter-physician variability in treatment regimens and dosages. Acute gout flares are treated with various agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, and – more recently – interleukin-1 inhibitors. These medications can also be used as prophylaxis if urate lowering therapy (ULT) is initiated. While these drugs can be used in patients with gout and CKD, there are often factors that complicate treatment such as the numerous medication interactions involving colchicine as well as the impact of glucocorticoids on common comorbidities like diabetes and hypertension. ULT is recommended to treat recurrent flares, tophaceous deposits, and in those with moderate-to-severe CKD with a serum urate goal < 6 mg/dL recommended to prevent flares. While many misconceptions exist around the risks of using urate-lowering agents in patients with CKD, there is some evidence that these medications can be used safely in individuals with renal impairment. Additional questions exist as to whether gout treatment is indicated for individuals on renal replacement therapy. Furthermore, there is conflicting data on whether ULT can impact renal function and cardiovascular disease in patients. All of these factors contribute to the unique challenges physicians face when treating patients with gout and CKD.
The current diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to different genetic and epigenetic backgrounds. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Stem-like molecules have the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N = 21) obtained from colectomies and 5 μm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N = 8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher (p = 0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase (p = 0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p<0.0001). These results suggest HURP's potential as a tumor marker in CRC. ZEB1 mRNA expression in tumors did not differ from that observed in normal adjacent tissue; moreover, a tendency of mRNA to a decrease (n.s.) was observed. IHC for ZEB1 showed immunostaining in all analyzed cases. Weak staining was observed in both tumor and stroma (average intensity score = ++, n.s.). Further stratification of patients by race revealed that in Caucasian-American (CA) patients, staining of ZEB1 was less likely to be associated with disease progression or death after at least 2 years of follow-up. Interestingly, samples obtained from African-American (AA) individuals, known to have worse CRC outcomes, had an association between ZEB1 presence and poor survival regardless of the immunostaining intensity. These findings suggest that IHC localization of ZEB1 may represent a marker of a poor CRC prognosis, particularly in AA patients. However, one must be careful not to over-interpret these results as a Fischer's Exact test revealed a non-significant p value = 0.387. Overall, we have identified two stem cell-like molecules, HURP and ZEB1, with potential as markers of aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. Future goals include collecting additional samples and expanding the project to examine other potential prognostic markers through IHC analysis of tissue microarrays. Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christopher Lahr, Christian R. Gomez. Emerging prognostic biomarkers in colorectal cancer: HURP and ZEB1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4918.
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