non-AA Patients Research Articles

Graft outcomes in pediatric kidney transplantation: Focus on the role of race

While significant racial disparities in graft outcome persist among adult and pediatric kidney transplant recipients in the US, some international studies do not show these differences. The aim of this study is to examine predictors of graft outcomes and the impact of race in our pediatric kidney transplant cohort. Records of 109 pediatric kidney transplant recipients performed at our institution between 7/99 and 4/07 were studied. Patients were grouped based on race: African-American (AA) vs. non-AA. Fifty-five AA (12 ± 5 years) and 54 non-AA patients (11 ± 6 years) were studied. There were more females, pre-emptive transplants and living donors in the non-AAs. Survival analysis showed significantly higher rejection rates in AAs, P = 0.02, and lower unadjusted graft survival (P = 0.09). Cox Proportional Hazards Survival Regression Analysis revealed biopsy-proven acute rejection and delayed graft function contributed to worse graft survival, while pre-emptive transplantation had a favorable effect. Race was not an independent risk factor for decreased graft survival in the final model. In conclusion, our cohort showed several modifiable risk factors that can partially account for poorer graft survival in pediatric AA kidney transplant recipients.

P2-14-01: Race, Response to Chemotherapy, and Outcome within Clinical Breast Cancer Subtypes.

Abstract Introduction: Racial disparity in breast cancer (BC) outcome has been attributed to access to care, socioeconomic factors, and biologic factors. In particular, the prevalence of triple negative BC is significantly higher among African-American (AA) women than white women (non-AA). However a recent population-based study suggests that racial disparities persist even if stratified by subtype, although it is possible that bias in stage at presentation may have influenced these results. In this study, we examined 464 women of uniform clinical stage II-III breast cancer, all treated with neoadjuvant chemotherapy, and examined pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS) to see if racial disparity exists within a more homogeneous stage and treatment cohort. Methods: The UNC Neoadjuvant Breast Cancer Database is a prospectively maintained cohort with clinical and outcome annotation. We identified women diagnosed between 1991–2011 and assigned BC subtype by clinical assay for estrogen receptor and progesterone receptor (hormone receptors, HR) and HER2. Fisher's Exact and Wilcoxon Rank sum tests compared characteristics between AA and non-AA. The Kaplan-Meier method and Log Rank test compared OS and RFS curves. Results: 142 (31%) of 464 women were AA, 294 (63%) were white, and 28 (6%) were other races (for analysis white and “other” were categorized as non-AA). 191 (41%) were clinical stage II and 273 (59%) stage III at diagnosis. Stage at diagnosis did not differ between AA and non-AA (p=0.07). AA were slightly older (median age 49 v 45, p=0.01) and were more likely to be HR-/Her2- (44% v 25%, p=0.003). All patients received preoperative chemotherapy. AA received less biologic therapy such as trastuzumab or on-protocol bevacizumab (10% v 18%, p=0.03) and received significantly less endocrine therapy (46% v 59%, p=0.01) than non-AA patients. 102 (22%) of patients had a pCR to neoadjuvant chemotherapy; pCR rates did not differ significantly by race (p=0.7) or within subtype by race (all p>0.14). At a median follow-up of 4.5 years, 121 (26%) of patients have died. Among HR-/HER2− (n=114) and HR-/HER2+(n=47) patients, OS and RFS did not differ between AA and non-AA (all p>0.5). Conversely, among HR+/HER2− patients (n=159) AA had worse OS (p=0.01) and RFS (p= 0.03) and among HR+/HER2+ patients (n=53), AA had worse OS (p=0.0004) and RFS (p=0.005). Conclusion: In this cohort of clinical stage II-III BC patients, AA women were over 75% more likely to have triple negative BC than non-AA patients. Pathologic reponse to chemotherapy did not differ between AA and non-AA patients. Examining the entire cohort, AA women had worse RFS and OS, however there was no difference among ER-negative subtypes. The difference in RFS and OS was driven by worse outcome among women with ER or PR+ tumors (regardless of HER2). It is possible that this racial disparity in outcome among hormone receptor-positive BC patients reflects unknown biologic differences by race, or differences in access to or receipt of endocrine therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-01.

Favorable Responses to Novel Agents for Multiple Myeloma in African American Patients,

Abstract 4213Multiple myeloma (MM) accounts for 10% of hematologic malignancies in the U.S. African Americans (AA) have twice the risk of developing multiple myeloma and, in previous studies, a higher mortality rate when compared to non-African Americans (non-AA). In recent years, clinical outcomes for patients with MM have improved as a result of new agents, such as immunomodulatory drugs (IMiDs) and bortezomib. However, the therapeutic impact of these new therapies in AA vs. non-AA patients has not been evaluated. In this study, 53 consecutive patients (23 AA, 30 non-AA) with newly diagnosed MM were retrospectively analyzed after induction treatment with thalidomide/dexamethasone (n=22), lenalidomide/dexamethasone (n=8), bortezomib/dexamethasone (n=5), bortezomib/thalidomide/dexamethasone (n=3), lenalidomide/bortezomib/dexamethasone (n=12), or an IMiD plus melphalan (n=3). AA and non-AA patients were comparable for age, immunoglobulin isotype, MM stage of disease, serum β2microglobulin and albumin levels, and cytogenetic abnormalities including del13 (27% vs. 38%, respectively, p=NS). When measured according to international uniform criteria, the response rate to induction therapy was not statistically different between AA and non-AA patients: complete remission (CR, 22% vs. 21.4%), very good partial remission (VGPR, 26% vs. 21.4%), or partial remission (PR, 43.4% vs. 32.1%). However, the rate of stable/progressive disease following induction therapy was significantly higher in non-AA patients (p = 0.03). Of 53 patients, 34 received high-dose chemotherapy followed by autologous stem cell transplant (ASCT). In this group, the CR + VGPR rate following ASCT was significantly higher in AA compared with non-AA patients (59% vs. 35%, p=0.0007). At a median follow up of 47 months, the relapse rate was 59% in AA and 46% in non-AA patients (p=NS) and the median time to progression (TTP) was 9.1 months in both groups. Five patients (9%) died. All deaths occurred in the non-AA cohort and in 4/5 cases death was due to disease progression. In conclusion, our findings demonstrate that despite their increased disease risk, AA patients with MM have a favorable outcome that is equivalent to that of non-AA patients when treated with IMiDs and/or bortezomib. Disclosures:No relevant conflicts of interest to declare.

Abstract P122: African-American Patients Presenting With Unexplained Syncope Have Significantly Worse 1-Year Outcome When Compared to Non-African Americans

Background: Syncope results in emergency department (ED) visits and hospital admissions. African-American (AA) patients often have multiple co-morbidities that translate to poorer outcome. We thought to evaluate the effect of AA race on outcome in patients with unexplained syncope. Methods: We evaluated 902 consecutive patients with unexplained pre-syncope/syncope between September 2007 and January 2009; all patients were enrolled in a prospective institutional registry. The primary endpoint was a composite of readmission for syncope, myocardial infarction (MI), stroke or death. In this study, we compared the outcome of AA to non African-American patients (non-AA). Results: There were 252 (28%) AA patients and 650 (72%) non-AA patients. When compared to non-AA patients, AA patients were older (64 ± 20 years vs. 59 ± 23 years, p<0.001) and likely to have hypertension (69% vs. 47%, p<0.001), diabetes (27% vs. 15%, p<0.001), heart failure (12% vs. 5%, p<0.001), and coronary disease (18% vs. 14%, p=0.01). During a follow-up period of 303 ± 140 days, the composite endpoint was observed in 92 (10.2%) patients and included 13 (1.4%) deaths, 5 (0.7%) strokes, 29 (3.2%) MIs and 45 (5%) syncope readmission. Multivariate regression analysis showed history of CAD (OR=1.9 95%CI 1.11-3.12), hypertension (OR=1.8 95%CI 1.03-3.43), diabetes (OR=1.7 95%CI 1.02-2.78) and AA race (OR=2.1 95%CI 1.30-3.28) to be predictors of worse outcome. Conclusions: African-American patients presenting with unexplained syncope have significantly worse 1-year outcome than non-AA. This is likely due in part to a higher incidence of significant co-morbidities in AA patients.

1159 SERUM ZINC BUT NOT SERUM VITAMIN D LEVELS ARE ASSOCIATED WITH DISEASE SEVERITY AND TREATMENT RESPONSE IN CHRONIC HEPATITIS C VIRUS INFECTION

G-1a patients achieved SVR compared to 26% G-1b (OR G-1a vs G-1b 1.097, p = 0.799). There were 84 African American (AA) patients included in the study, (44% G-1a and 53%G-1b). SVR rates were no different between subtypes with 17% of G-1a AA patients achieving SVR compared to 11% G-1b. 37% G-1a vs. 42% G-1b non-AA achieved SVR. The odds of obtaining SVR was significantly lower for AA vs non-AA patients (OR AA vs. non-AA 0.253, p = 0.0006.) Conclusions: G-1b subtype is common among AA patients and offers no advantage to treatment with PEG+RBV.

Combined Modality Therapy for Rectal Cancer: Analysis of Potential Differences in Disease Presentation, Treatment Adherence, and Treatment Outcome According to Race

Population-based studies suggest that African Americans (AAs) with rectal cancer have a worse overall outcome compared to whites. This relationship was explored in a cohort of locally advanced rectal cancer patients treated with preoperative chemoradiation (CRT) and surgery at two urban academic cancer centers. A total of 146 patients underwent curative-intent combined modality therapy for adenocarcinoma of the rectum. The median age was 57 years. Median dose was 50.4 Gy, given with 5-flourouracil based concurrent chemotherapy. Analysis was performed to test for differences in disease presentation, adherence to recommended therapy, and treatment outcome (freedom from failure, FFF) by race. Median follow-up was 34 months from completion of chemoRT. Twenty-six patients (18%) were AA, and 120 (82%) patients were White, Asian, or Hispanic. AA patients had longer times from diagnosis to start of therapy (median 45 days vs. 35 days, p < 0.01) and from CRT completion to surgery (median 42 days vs. 46 days, p = 0.03). CRT treatment time was no different between the two groups (median 38 days for both groups, p = 0.53). In the subset of patients with preoperative staging by endoscopic ultrasound (EUS, n = 119), AA patients presented with more favorable disease (20% stage I, 47% stage II, 33% stage II) compared with non-AA patients (0% stage I, 50% stage II, 48% stage III, 2% stage IV, p < 0.01). Among patients with stage II-IV disease (n = 116), the rate of any T or N downstaging was lower for AA patients (58% vs. 79%, p = 0.13). Pathologic complete response rates were also lower (17% vs. 26% for non-AA patients, p = 0.47), although not statistically different. AA patients were less likely to receive adjuvant chemotherapy (58% vs. 89%, p = 0.01). Log-rank analysis showed that time from diagnosis to therapy, and time from CRT to surgery were not associated with any difference in FFF when stratified by the median value. Similarly, completion of adjuvant chemotherapy was not associated with FFF. Overall, AA patients were not more likely to recur after therapy (FFF-3y, 100% for AA patients vs. 81% for non-AA patients, p = 0.09). This analysis reflects differences in time from preoperative therapy to surgery and a lower rate of adjuvant therapy in AA patients with rectal cancer treated in at two urban academic cancer centers. These differences did not appear to result in inferior disease outcome for this cohort. Further study is necessary to explore the reasons underlying the delays in therapy and lower rates of adjuvant chemotherapy for AA patients.

Association of black race and outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC): Results from a U.S. local oncology practice.

6107 Background: TNBC carries a poor prognosis. African American (AA) race has been shown as an adverse prognostic factor in many cancers. The objective of this study was to evaluate, in a real-world context, the impact of AA on disease recurrence and survival among nonmetastatic TNBC patients treated with adjuvant chemotherapy (CT). Methods: The Georgia Cancer Specialist Database (2003- 2008) was used. Patients with stage (I-III) BC, confirmed TN status, treated with adjuvant CT were followed from initial BC diagnosis to the earliest of death, BC recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). The secondary outcome was recurrence. DFS and recurrence were compared between AA and non-AA groups with Kaplan-Meier curves. The impact of AA status was further examined using multivariate Cox models adjusting for age, comorbidity, BMI, smoking status, initial BC stage, surgery, and radiation therapy. Results: Among 209 TNBC patients, 89 (42.6%) were AA. The two groups (AA vs. non-AA) were similar in mean age at BC diagnosis (53.2 vs. 54.4, p = 0.487), surgery and radiation rates (98.9% vs. 100%, p = 0.244; 68.5% vs. 62.5%, p = 0.365, respectively). Compared to non-AA, AA patients were more obese (BMI: 30.4 vs. 28.6, p=0.048), and more likely to be diagnosed at stage II (stage I: 31.5% vs. 51.7%; stage II: 64.0% vs. 43.3%; stage III: 4.5% vs. 5.0%; p = 0.0107). Compared to non-AA, AA patients had lower 5-year DFS rate (45.2% vs. 79.7%, p = 0.0005), and higher 5-year recurrence rate (42.5% vs. 7.0%, p = 0.0005). The median DFS was significantly shorter for AA than non-AA patients (615 vs. 775 days, p = 0.0005). The multivariate Cox models showed that AA was associated with lower likelihood for DFS (HR = 0.15, p = 0.0005), and higher risk for recurrence (HR = 8.16, p = 0.0006), compared to non-AA patients. Conclusions: This study suggested that AA race was associated with worse outcomes irrespective of later stage at presentation among TNBC patients who were treated with currently available adjuvant CT. Future studies need to explore genotypic as well as behavioral reasons for inferior outcomes associated with AA race. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis

Atypical Antipsychotic Medications Are Independently Associated With Severe Obstructive Sleep Apnea

Atypical antipsychotic (AA) medications are widely prescribed for their Food and Drug Administration-approved uses (acute mania, bipolar mania, psychotic agitation, bipolar maintenance, etc) and off-label indications. Although AA medications are associated with substantial weight gain, their tranquilizing effects may independently contribute to risk of obstructive sleep apnea (OSA) perhaps, by a reduction in activity of hypoglossal or recurrent activity of laryngeal nerve on the upper motor airway musculature. We hypothesized that AA medications are associated with more severe OSA independent of weight and neck circumference. Medical intake data and polysomnographic studies of patients referred to community hospital sleep disorders center were analyzed retrospectively. Mean age of patients was 49.1 years, 55.1% were male, and mean body mass index (BMI) was 33.8 kg/m. Sixty-eight patients (8.1%) were taking AA at the time of polysomnography. There were no differences in age, sex, neck circumference and BMI of AA versus non-AA patients. The mean (SE) apnea-hypopnea index values were 29.2 (3.5)/h in AA patients and 21.3 (0.8)/h in non-AA patients (P = 0.03). Thirty-four percent of AA patients had severe OSA (apnea-hypopnea index > 30/h) compared with 23% of non-AA patients (P = 0.04). When adjusted for BMI, sex, and use of benzodiazepines and sleeping aids, the odds ratios of severe OSA in AA patients were 1.9 times in non-AA patients (95% confidence interval, 1.1-3.3). Atypical antipsychotic medication use may increase the risk of more severe OSA independent of weight and neck circumference.

Abstract 3029: A KRAS microRNA binding site polymorphism as a novel biomarker of risk in triple negative breast cancer

Abstract The purpose of our study is to determine the role of a previously identified novel germline polymorphism in the let-7 miRNA binding site in the 3’UTR of the KRAS oncogene, referred to as the KRAS-variant, as a biomarker of breast cancer risk. We have shown that the KRAS-variant is a biomarker of increased risk of ovarian cancer for patients from families with Hereditary Breast and Ovarian Cancer. Thus, in this study, we tested the association of this biomarker with breast cancer using: i) A BC case-control recruited at Yale, ii) A cohort of Irish Caucasian women diagnosed with known BC subtypes and iii) A cohort of triple negative (TN) BC patients at Yale, all with known demographics and clinical variables. We assayed for the prevalence of the KRAS-variant by SNP genotyping to determine its association with BC. We compared the prevalence of the KRAS-variant in different BC subtypes and evaluated the association with age and ethnicity. MiRNA profiling was performed on the subjects in the TN BC cohort using Taqman low density miRNA microarrays. We analyzed the miRNA expression patterns within the TN BC cohort and also compared the miRNA expression patterns in the KRAS-variant positive and negative patients also evaluating the association with the age and ethnicity using linear modeling methods. We are currently performing gene expression analysis on the same TN BC patients that we have miRNA expression analysis and KRAS-variant testing completed on. We will compare gene expression patterns with the unique miRNA signatures in the KRAS-variant positive versus negative cases. We plan to use network programs to evaluate similarities in gene expression by miRNA, and also evaluate known targets of misexpressed miRNAs and determine their levels. In the BC case-control the KRAS-variant was found to be significantly associated with the ER/PR- BC patients below 51 yrs (33% vs. 10.5% for controls and ER/PR+). In the Irish Caucasian BC cohort the KRAS-variant was most prevalent in the TN BC patients (21.7% vs. 12-14% for Luminal A and Bs) below 51yrs. Consistently in the TN BC cohort the KRAS-variant was most prevalent in non-African American (AA) women below 51 yrs (33% vs. 21.5% in women of all races below 51 yrs). Through miRNA profiling we found that miRNA signatures vary across the TN BC patients, suggesting the existence of different groups within the TN cohort itself. The young non-AA TN BC patients appeared to have lower miRNA expression overall and clustered together. We also found that the KRAS-variant is associated with a unique miRNA expression pattern in TN BC patients with the variant compared to those without. A miRNA binding site polymorphism in the 3’UTR of the KRAS gene, the KRAS-variant, is a new biomarker of risk for developing triple negative BC in young non-AA women. In addition, KRAS-variant patient tumors have unique miRNA signatures and preliminary data supports they also have common gene expression differences. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3029.

1068 FUNCTIONAL OUTCOMES IN AFRICAN-AMERICANS AFTER ROBOTIC-ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 20101068 FUNCTIONAL OUTCOMES IN AFRICAN-AMERICANS AFTER ROBOTIC-ASSISTED RADICAL PROSTATECTOMY G. Joel Decastro, Gautam Jayram, Sergey Shikanov, Aria Razmaria, Gregory P. Zagaja, and Arieh L. Shalhav G. Joel DecastroG. Joel Decastro More articles by this author , Gautam JayramGautam Jayram More articles by this author , Sergey ShikanovSergey Shikanov More articles by this author , Aria RazmariaAria Razmaria More articles by this author , Gregory P. ZagajaGregory P. Zagaja More articles by this author , and Arieh L. ShalhavArieh L. Shalhav More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2192AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have demonstrated differences in surgical outcomes following radical prostatectomy based on ethnicity. We compared sexual and urinary outcomes in African American (AA) patients following robotic-assisted radical prostatectomy (RARP) to non-AA patients. METHODS We reviewed a prospectively maintained database for patients who underwent RARP at our institution with at least 12 months of follow-up. Erectile function was defined using question #23 from the UCLA Prostate Cancer Index (PCI) (as “enough for masturbation” or “enough for intercourse”), while urinary continence was defined as being “pad-free” on question #14. Only patients who were potent and pad-free preoperatively were included in the analysis. Multivariate logistic regression was used to compare post-operative potency and urinary pad-free status between AA and non-AA patients. RESULTS A total of 139 AA and 639 non-AA patients fitting the selection criteria were included in our analysis. Preoperative clinical variables and post-operative results are listed in Table 1. At 6 and 12 months post-operatively, AA patients had significantly lower potency rates compared to non-AA patients after controlling for age at diagnosis, clinical stage, biopsy Gleason grade, preoperative PSA, degree of nerve-sparing, BMI, and comorbidities (p=0.007, OR 0.41, CI 0.22-0.79). Similarly, we found a lower incidence of pad-free status for AA patients at 6 months and 12 months post-operatively after controlling for age, preoperative IPSS score, clinical stage, biopsy Gleason grade, preoperative PSA, and BMI (p=0.002, OR 0.47, CI 0.29-.076). PREOPERATIVE VARIABLES AA Non-AA Mean BMI 28.3(17.9-48.9) 28.2(18-49.1), p=0.99 Preop PSA, ng/ml (range) 6.8(6.2-7.4) 6(5.7-6.3), p=0.5 Clinical Stage T1 100(75%) 482(75%) T2 33(25%) 157(25%) Preop Gleason Score 6-7 128(96%) 595(93%) 8-10 4(4%) 43(7%) OUTCOMES at 6 MONTHS AA Non-AA Urinary Continence (UCLA PCI Q14) ≥3 pads daily 9(7.8%) 34(6.5%) 1-2 pads daily 50(42.7%) 204(39%) No pads 58(49.6%) 284(54.3%) Erectile Function (UCLA PCI Q23) None 34(25.6%) 107(16.8%) Not enough for sex 29(21.8%) 91(14.2%) Enough only for masturbation 26(19.5%) 187(29.3%) Enough for intercourse 44(33.1%) 253(39.7%) OUTCOMES at 12 MONTHS AA Non-AA Urinary Continence (UCLA PCI Q14) ≥3 pads daily 7(6.8%) 13(2.3%) 1-2 pads daily 39(37.9%) 161(27.9%) No pads 57(55.3%) 404(69.9%) Erectile Function (UCLA PCI Q23) None 18(20.5%) 60(12.0%) Not enough for sex 16(18.2%) 61(12.2%) Enough only for masturbation 20(22.7%) 156(31.1%) Enough for intercourse 34(38.6%) 225 (44.8%) CONCLUSIONS After controlling for relevant pre- and intra-operative variables, African American men appear to have worse urinary and sexual outcomes at 12 months following RARP compared to non-AA patients. Further studies are needed to validate these results as well as long-term functional outcomes after RARP. Chicago, IL© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e416 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information G. Joel Decastro More articles by this author Gautam Jayram More articles by this author Sergey Shikanov More articles by this author Aria Razmaria More articles by this author Gregory P. Zagaja More articles by this author Arieh L. Shalhav More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Demographic Differences Affecting the Decision to Defer Treatment for Chronic Hepatitis C (Chcv) Infection

Purpose: We have previously compiled data on 115 eligible treatment-naïve CHCV patients who elected to defer therapy [Dig Dis Sci 2007;52:1168–76]. Nearly all patients were asymptomatic, genotype 1, and had mild histologic disease. To assess which demographics affected expectant management after 3 years, a follow-up questionnaire was administered. Methods: Patients were asked their current health status, satisfaction with deferring pegylated interferon/ribavirin (PEG/RBV) using a 2 point Likert scale (not satisfied/satisfied), and whether they had reconsidered their decision to be followed expectantly. An attempt was made to reach all 74 patients from the 2-year cohort. Results: 38 (16 men; mean age 55 years, 17 > age 55; 19 African-Americans [AA]) out of 74 patients (51%) from the 2nd year cohort were contacted. 2 patients had died, 2 refused to answer, and 32 patients were lost to follow-up (43%). 31 out of 38 (82%) responders stated that they were still satisfied with their decision for expectant management. The proportion of non-AA to AA patients continuing to defer treatment (16 [52%] vs. 15 [48%]) was similar to the percentage at 2 years (53% vs. 47%) and 1 year (55% vs. 45%). Men were less likely to continue to defer treatment than women (13 [42%] vs. 18 [58%]), which was similar to proportions seen at the end of 2 years (44% vs. 56%) and 1 year (43% vs. 57%). Patients aged <55 deferred treatment more often than those >55 (17 [55%] vs. 14 [45%]), P= 0.02 compared to 2 year (58% vs. 42%) follow-up and P= 0.02 compared to 1 year (77% vs. 23%) follow-up. Conclusion: A majority of the patients contacted at 3 years with clinically mild genotype 1 CHCV infection remain satisfied with their initial decision to defer treatment. The percentage of younger patients continuing to choose expectant management continued to decline significantly compared with older patients, while older patients are choosing expectant management more often. The patient age variable was statistically significant between years 1 to 2 and 1 to 3. Only a trend was observed for race, where non-AA patients continued to choose expectant management, despite higher rates of sustained viral response (SVR), compared to AA patients (P= 0.5); and for gender where men continue to revisit their decision more frequently than women (P= 0.5). These patients will continue to be followed to determine if theses trends continue.Figure

Glucocorticoid receptor expression in breast cancer associates with older patient age

Breast cancer can be classified according to estrogen (ER), progesterone (PR), and HER2 receptor expression. Recent evidence suggests that activation of the glucocorticoid receptor (GR) contributes to breast cell survival, although the incidence of GR expression in primary human breast tumors is not well established. We therefore evaluated ER, PR, HER2, and GR by immunohistochemistry from 231 patients and found that while African American (AA) patient tumors were much more likely to be ER negative compared to tumors from non-AA patients, GR expression was significantly higher in tumors from patients >or=50 regardless of ancestry. Prospective examination of GR expression in tumors should be considered to determine whether GR contributes to long-term clinical outcome.

Primary Sclerosing Cholangitis Is a More Common Indication for Orthotopic Liver Transplantation among African American Than Non-African American Patients

Purpose: Primary sclerosing cholangitis (PSC) is a progressive, incurable condition of unknown etiology, characterized by inflammation, fibrosis, destruction and loss of interlobular-sized bile ducts, leading to biliary cirrhosis and liver failure. Orthotopic liver transplantation (OLT) is the only life-extending intervention for patients with end-stage PSC. Recent US Scientific Registry of Transplant Recipients (SRTR) data indicate that among patients with PSC being added to the United Network for Organ Sharing (UNOS) waiting list the proportion of African Americans (AA) was greater than non-AAs, compared to other disease indications. This suggests that PSC may run a more aggressive clinical course. It was our aim to determine whether the proportion of AA patients with PSC undergoing OLT per unit time was different from the proportion of non-AA patients undergoing OLT for PSC. Methods: The SRTR was reviewed between 1998 and 2002 inclusive for all adults (18 – 80 years) who were added to the UNOS waiting list for OLT. The proportions of AA and non-AA patients undergoing OLT for PSC within 1 year, 1–2 years, 2–3 years, and > 3 years of being added to the waiting list were calculated, and compared using the Chi-square test. Results: From 1998 to 2002 inclusive 39,878 patients were added to the UNOS waiting list for OLT. 2173 (5.45%) had PSC. Of these, 262 (12.1%) were AA. The proportions of AA patients with PSC who underwent OLT within 1 year, 1–2 years, 2–3 years, and >3 years of being added to the waiting list were: 28.2% (74/262), 13.7% (36/262), 8.8% (23/262) and 5.7% (15/262). 114/262 (43.5%) AA patients with PSC did not undergo OLT during the study period. The proportions of non-AA patients with PSC who underwent OLT within 1 year, 1–2 years, 2–3 years, and > 3 years of being added to the waiting list were: 33.5% (640/1911), 11.5% (220/1911), 4.7% (89/1911) and 4.9% (93/1911). 869/1911 (45.5) non-AA patients with PSC did not undergo OLT during this period. Except for the period < 1 year from the time of OLT listing, the proportion of AA patients with PSC undergoing OLT was significantly greater than the porportion of non-AA patients with PSC who underwent OLT (P= 0.026). Conclusion: These outcomes for AA patients with PSC suggest that their disease course may be more agressive, given that patients underwent OLT sooner from the time of listing than did non-AA patients. An alternative explanation is that AA patients with PSC were simply sicker than non-AA patients at the time of listing for OLT.

ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution

Human ICOS is a T cell costimulatory molecule supporting IL10 secretion. A pilot study investigating variations of the ICOS gene 3'UTR detected 8 polymorphisms forming three haplotypes (A, B, C). Haplotype-A and -C displayed the highest difference. Activated T cells from healthy AA homozygotes expressed significantly less ICOS and secreted more IL10 than AC heterozygotes, whereas AB heterozygotes displayed intermediate levels. Analysis of 441 multiple sclerosis patients and 793 controls showed that frequency of AA homozygosity was significantly lower in MS patients with relapsing–remitting onset ( N = 416) than in controls (OR = 0.70). Moreover, AA patients with relapsing–remitting onset had lower relapse rate and multiple sclerosis severity score than non-AA patients.

Prolonged responses after autologous stem cell transplantation in African-American patients with multiple myeloma

Multiple myeloma (MM) has a double incidence in African-American (AA) than in non-AA patients and previous studies have shown a higher mortality in the former patient population. Here, we retrospectively analyzed the results of autologous stem cell transplantation (ASCT) in 38 AA and 32 non-AA consecutive patients. The two groups were comparable at diagnosis for age, stage of the disease, cytogenetic abnormalities, beta(2) microglobulin and albumin blood levels, and plasma cell marrow infiltration. The rates of complete and partial response observed in AA and non-AA patients after induction chemotherapy (9 and 42 vs 13 and 33%) and at 2 months (31 and 25 vs 30 and 20%) following ASCT were similar. At 6 months after ASCT, a greater relapse rate was observed in non-AA patients (P=0.009). At a median follow-up of 26 months, AA patients had a greater event-free survival (P=0.02) than non-AA patients, whereas overall survival was comparable in the two groups. The initial finding that AA patients with MM, compared to non-AA patients, had more prolonged responses and comparable survival after ASCT suggests that intensified chemotherapy is equally effective in patients of various ethnicities.

Predictors of enrollment in lung cancer clinical trials

Clinical trials may offer patients innovative therapeutic options with potentially better outcomes, which are particularly relevant for patients afflicted with lung carcinoma, because current therapies provide only modest survival benefits. Only approximately 5% of patients with newly diagnosed cancer participate in clinical trials nationwide, and African-American (AA) patients are particularly under-represented. To determine predictors of clinical trials enrollment, the authors reviewed the medical records of 427 patients with lung carcinoma (175 AA patients and 252 non-AA patients) who were eligible for clinical trials between 1994 and 1998 at the Karmanos Cancer Institute in Detroit, Michigan. Logistic regression analysis was used to assess the association of patient demographic characteristics and clinical trial enrollment. Ninety-one patients (21%) were enrolled onto a lung cancer clinical trial during the period of the current study. Enrollment was associated significantly with race (P < 0.001), gender (P = 0.048), age (P = 0.005), and insurance type (P = 0.024). After multivariable adjustment, only race and gender remained significant predictors of enrollment. AA patients were less likely to enroll than non-AA patients (odds ratio [OR], 0.485; 95% confidence interval [95% CI], 0.243-0.966), and men were more likely than women to enroll (OR, 1.812; 95% CI, 1.033-3.178). The current results suggest disparities by race and gender in the enrollment of patients onto lung cancer clinical trials and support the need to improve educational and outreach endeavors that would make clinical trials available to a wider range of eligible patients.

African American Patients with Multiple Myeloma Have Prolonged Responses after Autologous Stem Cell Transplantation.

The incidence of multiple myeloma (MM) in African American (AA) patients is higher than in other racial groups. In this retrospective study we analyzed the outcome of 70 consecutive patients (AA n=38, non-AA n=32) with MM receiving an autologous stem cell transplantat (ASCT) at the University of Illinois at Chicago. No significant differences, including age, gender, stage of disease, Hgb and b2 microglobulin levels, skeletal involvement, plasma cell marrow infiltration, were observed between AA and non-AA patients at diagnosis. Chemotherapy prior to ASCT was also comparable in the two groups. Conditioning regimen with high dose melphalan was used in 84% AA and 72% non-AA, while the remaining patients received BCNU/melphalan. After induction chemotherapy no difference occurred in complete remission (CR) and partial remission (PR) rates in AA (9% and 42%) as compared to non-AA (13% and 33%). Two months after transplantation CR and PR rates were 31% and 25% in AA and 30% and 20% in non-AA. However, at 6 months after ASCT 25%AA vs 60% non-AA patients showed a progression of the disease (p=0.009). At a median follow-up of 26 months (range:1 to 89), 79% AA and 69% non-AA patients are alive. The estimated median Event-Free-Survival in the two groups is 21 vs 12 months (p=0.02), while the estimated median Overall Survival is 64 vs 39 months (p=0.19) (Figure 1). In conclusion, AA and non-AA patients have similar CR and PR rates after ASCT. However, AA patients seem to have more prolonged clinical responses. In a setting where equal access to modern modalities of treatment is available, race does not appear to affect responses to therapy in multiple myeloma. [Display omitted]

Osteopontin gene haplotypes correlate with multiple sclerosis development and progression

Osteopontin (OPN) is an inflammatory cytokine highly expressed in multiple sclerosis (MS) plaques. In a previous work, we showed that four OPN polymorphisms form three haplotypes (A, B, and C) and that homozygotes for haplotype-A display lower OPN levels than non-AA subjects. In this work, we evaluated the distribution of these OPN haplotypes in 425 MS patients and 688 controls. Haplotype-A homozygotes had about 1.5 lower risk of developing MS than non-AA subjects. Clinical analysis of 288 patients showed that AA patients displayed slower switching from a relapsing remitting to a secondary progressive form and milder disease with slower evolution of disability. MS patients displayed increased OPN serum levels, which were partly due to the increased frequency of non-AA subjects. Moreover in AA patients, OPN levels were higher than in AA controls and similar to those found in both non-AA patients and controls, which suggests a role of the activated immune response. These data suggest that OPN genotypes may influence MS development and progression due to their influence on OPN levels.

Androgens and liver tumors: Fanconi's anemia and non‐Fanconi's conditions

The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available data, because the number of patients receiving androgens is unknown.

Anaemia is common after kidney transplantation, especially among African Americans.

Anaemia is a major cardiovascular risk factor in renal disease. It might be appropriate to extrapolate this association of anaemia with cardiovascular disease to renal transplant recipients who continue to have a significant cardiovascular risk. There are very few studies addressing the issue of anaemia after renal transplantation. We studied 192 consecutive kidney transplant recipients over a 5-year period in a tertiary referral centre in Michigan, USA. Patients who were followed up at the ambulatory transplant clinic for at least 1 year after transplantation were studied. Haemoglobin (Hb) level at 6 months and 1 year after renal transplantation was recorded. Risk factors for anaemia were evaluated using multivariate regression analysis. Significant anaemia (Hb <11 g/dl in females and <12 g/dl in males) was common (19.3% at 6 months, 19.8% at 1 year). Anaemia was more common in African American (AA) than in non-AA patients both at 6 months and 1 year after transplantation. Multivariate analysis showed that serum creatinine was an independent risk factor for anaemia. Female gender was associated with significant anaemia at 1 year. Intriguingly, AA race was also an independent risk factor at 6 months and strong trend for risk at 1 year. Anaemia is common during the first year after kidney transplantation. AA race as well as high serum creatinine and female gender are independent risk factors for post-transplant anaemia. The importance of anaemia as a risk factor in AA patients after renal transplantation should be more recognised.