non-AA Patients Research Articles

Presentation and Management of Paroxysmal Nocturnal Hemoglobinuria: A Single-Center Experience

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis. Real-world experience of PNH management is largely unreported. A retrospective analysis was undertaken based on medical records from six patients with PNH [two with aplastic anemia (AA)] treated at our center, Dicle University, Turkey. Diagnosis was based on granulocyte PNH clones, ranging from 93% to 66%. All patients had symptoms consistent with PNH. One patient was managed adequately with supportive measures only. Five were treated with the complement inhibitor eculizumab. Follow-up data (<1 year) were available in four cases (the fifth had received only three infusions by final follow-up). Hemoglobin level in these four patients increased from 4.1-7.2 g/dL to 8.3-13.0 g/dL. Lactate dehydrogenase, a marker for hemolysis, decreased profoundly in the two non-AA patients, with more minor improvements in the two AA patients. Weakness and fatigue improved in all eculizumab-treated patients. Four of the five treated patients became transfusion independent, including the patient given only three infusions. In the remaining case, a patient with AA, transfusion requirement decreased, and abdominal pain and dysphagia resolved. No adverse events occurred. PNH can be successfully managed in routine practice.

Abstract 3714: Detroit African Americans (AA) are overrepresented among patients with large high-grade dysplastic (HGD) adenomas (LHiGDA) versus those with small HGD adenomas (ShiGDA)

Abstract Colorectal cancer incidence and mortality impacts African Americans more than other ethnic group. While causes for this disparity are likely multifactorial, etiology of carcinogenesis may be the most important. A better understanding of these factors might enable us to design interventions based on regional realities. In the context of screening trials we obtained data from a cohort of patients with high-grade dysplastic adenomas. We compared differences between those with large-sized (&amp;gt;1cm) and those with smaller lesions. Methods: Patients were selected on the basis of high CRC risk based on a brief questionnaire. Prior to colonoscopy, stool was submitted for FOBT and anti-adenoma antibody (Adnab-9) binding determined by ELISA. The colonoscopy outcomes were noted for the cross-sectional element of the study. The longitudinal component enabled collection of additional specimens to elucidate the source of the adenoma antigen. Pathology was reviewed and antigenic mapping of 6 colonic segments was performed by Adnab-9 immunohistochemistry. If any 2 contiguous colonic segments expressed the antigen the colon was deemed to have a field effect. Results: 49 Patients were found to have HGD lesions of whom 26 were AA (53%). All but 1 were male. Mean age±SD was 62±14.8 years. 28 (57%) had LHiGDA and the remainder ShiGDA. 69% AA had LHiGDA versus 29% in the ShiGDA group (OR 5.9 CI 1.7-20.9;p = 0.03). Intragroup age differences between the AA and non-AA patients were not statistically (NSS) different (66.3±8.3 versus 63.9±10.5 and 58.4±21.9 versus 61.07±9.9 years respectively). Intergroup age variation by race was NSS (AA p = 0.2 and non-AA p = 0.5). Likewise intergroup lesion size variations were NSS (p = 0.4 and p = 0.2 respectively). The proportions of TVA were also NSS between the groups (p = 1 and p = 0.2 respectively}. The stool Adnab-9 binding was also not significantly different (p = 0.5 and p = 0.9 respectively). There was however a significant difference between the 2 lesion groups in terms of the presence of a field effect which was performed in a small percentage (14.3 versus 33%) for the large versus the small lesions (100 vs 14.3% RR7 CI 1.1-43;p&amp;lt;0.02) but numbers were too small for intragroup calculations. Conclusions: AA are overrepresented in the LHiGDA group but there were no clues for differing pathways of carcinogenesis or for the differential dwell times of these lesions. We did not evaluate habits such as alcohol intake and smoking as risk factors which conceivably may play a role. The morphology of the lesion and pathway antigens suggest that the adenoma-carcinoma is the pathway of causation but these should be further studied to design effective intervention and screening. Screening is likely to better detect the large than the small lesions and this may be an advantage for the AA population who accordingly should be encouraged to actively participate in local screening programs. Citation Format: Martin Tobi, Fadi Antaki, MaryAnn Rambus, Paula Sochacki, Edi Levi. Detroit African Americans (AA) are overrepresented among patients with large high-grade dysplastic (HGD) adenomas (LHiGDA) versus those with small HGD adenomas (ShiGDA). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3714. doi:10.1158/1538-7445.AM2015-3714

African-American race modifies the influence of tacrolimus concentrations on acute rejection and toxicity in kidney transplant recipients.

To determine the effect of tacrolimus trough concentrations on clinical outcomes in kidney transplantation, while assessing if African-American (AA) race modifies these associations. Retrospective longitudinal cohort study of solitary adult kidney transplants. Large tertiary care transplant center. Adult solitary kidney transplant recipients (n=1078) who were AA (n=567) or non-AA (n=511). Mean and regressed slope of tacrolimus trough concentrations. Subtherapeutic concentrations were lower than 8ng/ml. AA patients were 1.7 times less likely than non-AA patients to achieve therapeutic tacrolimus concentrations (8ng/ml or higher) during the first year after kidney transplant (35% vs 21%, respectively, p<0.001). AAs not achieving therapeutic concentrations were 2.4 times more likely to have acute cellular rejection (ACR) as compared with AAs achieving therapeutic concentrations (20.8% vs 8.5%, respectively, p<0.01) and 2.5 times more likely to have antibody-mediated rejection (AMR; 8.9% vs 3.6%, respectively, p<0.01). Rates of ACR (8.3% vs 6.7%) and AMR (2.0% vs 0.9% p=0.131) were similar in non-AAs compared across tacrolimus concentration groups. Multivariate modeling confirmed these findings and demonstrated that AAs with low tacrolimus exposure experienced a mild protective effect for the development of interstitial fibrosis/tubular atrophy (IF/TA; hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.47-1.32) with the opposite demonstrated in non-AAs (HR 2.2, 95% CI 0.90-5.1). In contradistinction to non-AAs, AAs who achieve therapeutic tacrolimus concentrations have substantially lower acute rejection rates but are at risk of developing IF/TA. These findings may reflect modifiable time-dependent racial differences in the concentration-effect relationship of tacrolimus. Achievement of therapeutic tacrolimus trough concentrations, potentially through genotyping and more aggressive dosing and monitoring, is essential to minimize the risk of acute rejection in AA kidney transplant recipients.

Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.

305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.

HCV Triple Therapy is Equally effective in African-Americans and Non-African-Americans

Real-world experience with HCV medications differs from original the index studies. African-Americans (AA) are commonly underrepresented in clinical trials. Therefore, we hypothesized that postmarketing experience with the first generation HCV protease inhibitors (PI) (telaprevir and boceprevir) differs from premarket reports in clinically meaningful ways regarding patient race. We conducted a single-center, retrospective, observational analysis to evaluate the efficacy of HCV triple therapy in a nontrial setting. Clinical response and quantitative laboratory values were compared between AA and non-AA patients throughout the duration of treatment. Patients were included if they started triple therapy treatment after July 2011 and are not a part of any other clinical/pharmaceutical trials. Thirty-five patients with HCV genotype 1 were included in this study—22 non-AA and 13 AAs. AAs had a higher BMI compared to non-AA (33.6 vs 28.8, p = 0.046). “High” baseline HCV RNA values (above 800,000 copies) were more prevalent in AA (69.2 %) vs non-AA (63.6 %). AA had less favorable IL28B genotypes; only 7.7 % had type CC compared to 40.9 % of non-AA. SVR12 was achieved 82 % of the time with each PI but there was no significance in type of PI used (p = 1.00). Patients with cirrhosis were less likely to achieve SVR12 (40 %) compared to those without cirrhosis (88 %, p = 0.013). Thirty-three percent of the patients who received blood transfusions did not achieve SVR12 while every patient who did not require transfusion achieved SVR12 (p = 0.001). All patients with IL28B genotype CC achieved SVR12 (p = 0.007). SVR12 did not differ among AA (77 %) and non-AA (86.4 %) (p = 0.528).

CIRCULATING LEUCINE-RICH α-2-GLYCOPROTEIN glycoprotein 1 TO DETECT ACUTE APPENDICITIS IN PATIENTS WITH ACUTE ABDOMINAL PAIN

Objectives & BackgroundCirculating leucine-rich α-2-glycoprotein-1 (LRG1) protein has been found in the plasma and urine of patients with acute appendicitis (AA) and may be useful for diagnosis. The present study...

Evaluation of Racial Disparities in Pediatric Kidney Transplant.

Prior studies have demonstrated that socioeconomic status (SES) influences racial disparities in adult kidney transplant (KTX) recipients, but there are limited analyses studying this in pediatric KTX and a paucity of data examining psychosocial issues on racial disparities. METHODS: This was a longitudinal cohort study of all pediatric KTX (<21 yo) transplanted at a single-center between July 1999 and Dec 2013. Detailed sociodemographics, psychological, family and clinical variables were collected from medical records. Univariate and multivariable analyses were conducted to determine predominant differences between racial cohorts (African-American [AA] vs. non-AA) and factors associated with outcomes. RESULTS: 175 pediatric KTX were included, 46% were AA. On average, AA recipients lived closer to the transplant center (102±65 vs. 133±72 miles, p=0.004), were less likely to receive a living donor transplant (19% vs. 50%, p<0.001) and were on dialysis longer (1.0±0.9 vs. 0.6±0.8 yrs, p=0.006). After transplant, AA recipients were 3.4 times more likely to experience (95% CI 1.6-7.3) graft loss (see Figure 1). AA patients had higher mean SCr (2.6±2.5 vs. 1.2±0.7 mg/dL, p<0.001) and had higher rates of rejection (43% vs. 18%, p<0.001), medication non-adherence (26% vs. 12%, p=0.015), disruptions in parenting (12% vs. 1%, p=0.002), and family insurance/monetary issues (17% vs. 5%, p=0.011). After adjusting for donor type, DGF, acute rejection, SES and family issues, the influence of AA race on graft loss was significantly reduced, but not completely abrogated (adjusted OR 1.6 95% CI 0.7-4.1). Patients between 18-21 yo had a 50% higher risk of graft loss as compared to those <18 yo; however this risk was similar between AA and non-AA patients. CONCLUSIONS: Pediatric AA KTX patients continue to experience a disproportionately higher rate of graft loss, which is moderately explained by differences in donor type, immunologic risk, socioeconomics and family-related issues; however, these risks do not fully explain the racial disparities.Figure: No Caption available.

Early Graft Loss, Cardiovascular Risk Factor Control and African-American Disparities in Kidney Transplantation.

There is continued and significant debate regarding the salient etiologies associated with racial disparities in kidney transplant (KTX) recipients. Methods: This was a longitudinal cohort study of all adult KTX recipients, comparing African-American (AA) and non-AA recipients that had early graft loss (<5 yrs) to those with graft longevity (surviving graft with at least 5 yrs of follow-up). Results: 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). In the entire cohort, early graft loss was significantly associated with disability income (adjusted odds-ratio [AOR] 2.2, 95% CI: 1.1-4.5), kidney donor risk index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6). Unique risk factors in AAs included Medicare only insurance (AOR 8.0, 2.3-28) and BK infection (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control; AAs with a mean systolic BP <150 mmHg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while LDL <100 mg/dL (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dL (AOR 0.4, 0.2-1.0) and HgbA1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but not in non-AA recipients. The figure below demonstrates through ROC curve analysis that CV risk factors and control are predictive for graft loss in AA recipients (C-statistic 0.69, p<0.001), but not in non-AA patients (C-statistic 0.57, p=0.211).Figure: No Caption available.Conclusions: These results demonstrate that AA recipients have unique risk factors for early graft loss, suggesting that controlling CV comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation.

Kidney Transplant Survival After Early Corticosteroid Withdrawal: Impact of African American Race.

Background: We sought to compare outcomes related to transplant survival between AA and non-AA recipients after early corticosteroid withdrawal (CSW), and to contrast these outcomes with AA and non-AA patients maintained on corticosteroids (CSM) after kidney transplantation. Methods: We analyzed 405 consecutive solitary kidney recipients from 1/06 to 12/11, after excluding 5 patients with early death or graft thrombosis. All patients received 5 days of I.V. steroids along with tacrolimus/mycophenolate mofetil maintenance therapy. CSW was undertaken after 5 days in 269/405 (66%) patients. The remaining 136 CSM patients were considered higher risk due to delayed graft function, high HLA antibody sensitization, or previous transplant failure. AAs were similarly represented in the CSW and CSM groups (44% vs. 47%). Patient and allograft survival between races within each steroid group were analyzed using Kaplan-Meier methodology and Cox regression analysis. Results: Within the CSM group, there was no statistical difference in graft survival between AA and non-AA recipients (Figure 1a). Alternatively, AA’s exhibited worse survival in the CSW cohort, with a relative decline manifesting after three years post-transplantation (Figure 1b). This was despite similar long term acute rejection rates in AAs and non-AAs in the CSW group (25% vs. 19%, p=ns). Within the CSW group, AA recipients had a longer median dialysis vintage (62 mos vs. 12 mos, p<0.001), more deceased donor (DD) transplants (82% vs. 39%, p<0.001), and more HLA mismatches (4.48±1.48 vs. 3.42±2.00, p<0.001). After controlling for these differences, AA race did not independently predict allograft loss, but DD transplant did (HR: 2.83, 95%CI: 1.22-6.58, p=0.016). Conclusion: Among a large cohort of kidney recipients who underwent CSW, AA recipients had inferior allograft survival beyond three years. However, donor source appeared to drive differences seen between AA and non-AA recipients. Disparities in access to living donor kidney transplanatation may determine differences in outcomes after corticosteroid withdrawal.Figure: No Caption available.

Cardiac Transplantation in African Americans: A Single‐Center Experience

In view of limited data on the subject of graft and patient survival differences between African American (AA) and non-AA heart transplant recipients, we reviewed our experience. There is a higher mortality among AA recipients compared with non-AA recipients after cardiac transplantation. The study included all AA patients who have received a heart transplant in our center since 1983. Stepwise Cox regression was used for covariates affecting the survival. The χ(2) test was employed to identify the effects of a mechanical assist device and pretransplant creatinine (Cr) on the outcomes in AA and non-AA patients. Kaplan-Meier curves were used to examine survival. The average survival among AA recipients was 5.4 years, compared with 12 years for the non-AA recipients, with 1-, 5-, and 10-year survival rates of 80%, 55%, and 25%, respectively. This was found to be statistically inferior to the survival probabilities of 92%, 78%, and 58% for the non-AA group (P < 0.005). Based on stepwise Cox regression, the variables such as ethnicity (P < 0.05), pretransplant Cr (P < 0.05), presence of a mechanical assist device (P < 0.005), and United Network for Organ Sharing (UNOS) status at transplant (P < 0.05) independently predicted the outcomes. Kaplan-Meier analysis of pretransplant Cr level and survival showed that the AA group did significantly worse for all Cr classes. There is a statistically significant difference in outcomes between AA and non-AA patients after cardiac transplantation. African American patients have decreased survival over a period of time. Pretransplant Cr, ethnicity, presence of a mechanical assist device, and UNOS status at transplantation are independent predictors of outcomes.

Combined-modality Therapy for Rectal Cancer

Population-based studies suggest African Americans (AAs) with rectal cancer have a worse overall outcome compared with non-AAs. This relationship was explored in a cohort of rectal cancer patients treated with preoperative chemoradiation therapy (CRT) and surgery at 2 academic cancer centers. A total of 146 patients (26 AA, 120 non-AA) underwent treatment with curative intent. The median age was 57 years. Median dose was 50.4 Gy, given with 5-fluorouracil-based concurrent chemotherapy. Differences in disease presentation, adherence to recommended therapy, and treatment outcome (freedom from failure) by race were analyzed. Median follow-up was 34 months from completion of CRT. AAs had longer time from diagnosis to start of therapy (median, 45 vs. 35 d; P<0.01) and from CRT completion to surgery (median, 42 vs. 46 d; P=0.03). AA patients presented with more favorable disease (20% stage I, 33% stage III) compared with non-AA patients (0% stage I, 48% stage III, P<0.01). AA patients were less likely to receive adjuvant chemotherapy (58% vs. 89%, P=0.01). Log-rank analysis showed AAs were not more likely to recur after therapy (freedom from failure at 3 y, 100% for AA patients vs. 81% for non-AA patients, P=0.09). The difference in time from preoperative therapy to surgery and a lower rate of adjuvant therapy in AA patients did not seem 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.

Clinicopathological characteristics and outcomes of surgically excised renal masses in African Americans

ObjectivesIn the present study, we report on the clinical and pathological characteristics of African American (AA) patients with surgically excised renal masses and assess the associations between race and oncological outcomes. Methods and materialsWe conducted a retrospective review of patients who underwent partial or radical nephrectomy for renal masses at our institution between 2000 and 2010. Patients were divided into 2 groups based on self-reported race: AA and non-AA. Patient demographics and disease characteristics, and overall, cancer-specific, recurrence-free, distant, and local recurrence-free survival for localized renal cell carcinoma (RCC) were compared between AA and non-AA patients. Multivariable proportional hazard analyses were used to assess the associations of race with oncological outcomes. ResultsA total of 1,467 patients, of whom 359 (24.5%) were AA, were included. Rates of benign disease were comparable between AA patients and non-AA (18.2% vs. 17.6%, P = 0.556). AA patients presented with higher rates of localized disease (83% vs. 71%, P<0.001). Papillary subtype accounted for 40.8% of RCCs in AA patients compared with 11.6% in non-AA patients (P<0.001). The high proportion of papillary RCC in AA patients was maintained across disease stages. On univariable analyses, AA patients had better recurrence-free and cancer-specific survival. On multivariable analyses, AA race was not a significant predictor of oncological outcomes after adjusting for patient and disease characteristics. ConclusionIn this study, AA patients presented with more localized disease than non-AA patients, whereas rates of benign disease were comparable between the groups. Furthermore, AA patients had roughly 3 times higher rates of papillary RCC across disease stages. On univariable analyses, AA patients appeared to have more favorable oncological outcomes. However, this association is likely explained by tumor stage, grade, and histology as outcomes were similar across races when the analyses were adjusted for these and other characteristics.

Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four-yr data on 904 patients receiving tacrolimus and enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non-AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non-AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC-MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non-AA patients. Biopsy-proven acute rejection was higher in AA vs. non-AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non-AA patients. Kidney allograft survival remains lower for AA vs. non-AA recipients even under the current standard of care.

Acute appendicitis or not: Facts and suggestions to reduce valueless surgery

For suspected acute appendicitis (AA), risk stratification with clinical tools and supplemental imaging is useful for reducing unnecessary surgery and radiation exposure without increased appendicitis rupture. In patients receiving surgery for suspected AA, we compared adults versus children, and patients with versus without AA. Based on these facts and the benefits of surgery in patients without AA, we recommend a way to reduce unnecessary surgery. We retrieved the records of patients who underwent surgery for presumed appendicitis from January 2009 to December 2011. Risks of AA were assessed using the Alvarado score or the pediatric appendicitis score. We compared the adult and pediatric patients, and the patients with and without AA. The value of surgery for non-AA patients was evaluated by experts using the Delphi method. We enrolled 314 patients, which comprised 258 adults and 56 children. Adult patients had higher percentages of migratory abdominal pain and local tenderness. Pediatric patients had higher frequencies of anorexia, nausea, vomiting, and leukocytosis. Our pediatric patients had higher clinical scores than adults ( p < 0.001). The arrival-to-surgery time was shorter in children ( p = 0.040), whereas no significant difference was found in symptom-to-emergency department time or length of hospital stay. There were 15 adults and one child without AA. The non-AA adults had a lower percentage of local tenderness ( p = 0.040) and longer arrival-to-surgery times ( p = 0.015) and hospital stays ( p = 0.020). In the valuing of surgery, of the 16 patients eight were evaluated as indicated, six as helpful, and two as not helpful. Preoperative imaging studies should be considered in moderate-risk patients, especially when the clinical manifestations are ambiguous. More workups, or even a prolonged observation, but not rushing to the operation theater, should be undertaken for patients with unremarkable imaging. In high-risk patients, surgery was valuable for patients without preoperative imaging, or with suggestive but inconclusive imaging results.

TCT-343 Does The National Cardiovascular Data Registry Bleeding Risk Score Accurately Predict Bleeding In African American Patients Undergoing Percutaneous Coronary Intervention?

Background: The National Cardiovascular Data Registry (NCDR) risk score was validated to predict post-percutaneous coronary intervention (PCI) bleeding. However, this risk prediction model was derived from a predominantly Caucasian population, with an under-represented African American (AA) population of 6%. Differential post-PCI bleeding rates have been reported. Objectives: We aim to analyze the post-PCI bleeding events in a better-represented AA population, and to determine if the NCDR bleeding risk model is improved by the addition of AA race to predict post-PCI bleeding. Methods: From our own PCI registry, bleeding (defined by NCDR CathPCI registry as transfusion, prolonged hospital stay and/or drop in hemoglobin >3g/dL) rates were compared between AA and non-AA patients. A logistic regression model using ROC curves was used to compare the accuracy of the NCDR risk score in predicting post-PCI bleed in AA and non-AA patients, and a net reclassification improvement (NRI) analysis was used to determine...

Assessment of the Prognostic Value of Two Common Variants of BRCA1 and BRCA2 Genes in Ovarian Cancer Patients Treated with Cisplatin and Paclitaxel: A Gynecologic Oncology Group Study

Purpose: BRCA1/BRCA2 germline mutations appear to enhance the platinum-sensitivity, but little is known about the prognostic relevance of polymorphisms in BRCA1/BRCA2 in epithelial ovarian cancer (EOC). This study evaluated whether common variants of BRCA1/BRCA2 are associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced stage sporadic EOC.Experimental Design: The allelic frequency of BRCA1 (2612C > T, P871L-rs799917) and BRCA2 (114A > C, N372H-rs144848) were determined in normal blood DNA from women in Gynecologic Oncology Group protocol #172 phase III trial with optimally resected stage III EOC treated with intraperitoneal or intravenous cisplatin and paclitaxel (C + P). Associations between polymorphisms and PFS or OS were assessed.Results: Two hundred and thirty-two women were included for analyses. African Americans (AA) had different distributions for the two polymorphisms from Caucasians and others. For non-AA patients, the genotype for BRCA1 P871L was distributed as 38% for CC, 49% for CT, and 13% for TT. Median PFS was estimated to be 31, 21, and 21 months, respectively. After adjusting for cell type, residual disease, and chemotherapy regimen, CT/TT genotypes were associated with a 1.40-fold increased risk of disease progression [95% confidence interval (CI) = 1.00–1.95, p = 0.049]. After removing seven patients with known BRCA1 germline mutations, the hazard ratio (HR) was 1.36 (95% CI = 0.97–1.91, p = 0.073). The association between BRCA1 P871L and OS was not significant (HR = 1.25, 95% CI = 0.88–1.76, p = 0.212). Genotype distribution of BRCA2 N372H among non-AA patients was 50, 44, and 6% for AA, AC, and CC, respectively and there is no evidence that this BRCA2 polymorphism was related to PFS or OS.Conclusion: Polymorphisms in BRCA1 P871L or in BRCA2 N372H were not associated with either PFS or OS in women with optimally resected, stage III EOC treated with cisplatin and paclitaxel.

Abstract 18941: Vasodilator Use Guided by Wireless Pulmonary Artery Hemodynamic Monitoring Reduces Heart Failure Hospitalizations in Both African American and Non-African American Heart Failure Patients: Results from the CHAMPION Trial

Introduction: It is unknown whether benefits produced by nitrates and hydralazine (HDZ) in African Americans (AA) also occur in non-African American (non-AA) patients. The CHAMPION Trial showed that, compared to usual care (UC) patients, those managed according to wirelessly measured pulmonary artery pressures (w-PAP) plus UC had a significant reduction in heart failure (HF) hospitalizations over 6 months. The current analysis evaluated pattern of use and effects of nitrates and HDZ in AA and non-AA CHAMPION trial subjects to determine if non-AA patients receiving these vasodilators according to w-PAP will have benefits similar to those occurring in non-AA. Methods: Retrospective comparison of changes in use of nitrates and HDZ in AA and non-AA subjects randomized in the CHAMPION trial and evaluation of the effects of these therapeutic changes on HF hospitalization rates. Results: Of 424 non-AA patients, 202 were assigned to w-PAP and 222 to UC. Of 126 AA, 68 were assigned to w-PAP and 58 to UC. Baseline nitrate and HDZ use was similar between w-PAP and UC for both non-AA and AA groups. At 6 months nitrate use increased more in the w-PAP than UC group in both non-AA [90 (44.6%) vs. 48 (21.6%); p&lt; 0.0001] and AA [23 (33.8%) vs. 17 (29.3%); p=ns due to small sample size]. At 6 months HDZ use increased more in the w-PAP than UC group in both non-AA [39 (19.3%) vs. 27 (12.2%); p&lt; 0.0452] and AA [22 (32.4%) vs. 15 (25.9%); p=ns due to small sample size] . Within the non-AA population nitrate dose increased at 6 months more in the w-PAP than in the UC group (20.43 mg vs. 4.21 mg; p= 0.05). HF hospitalization rates were significantly lower in w-PAP than UC subjects both within the non-AA (0.31 vs. 0.43 p = 0.0007) and the AA population (0.33 vs. 0.45 p=ns due to small sample size) and the magnitude of reduction in HF hospitalization was similar for non-AA and AA subjects. Conclusions: Greater utilization of nitrates and HDZ in HF patients managed with w-PAP produces significant and similar reductions in HF hospitalizations in non-AA and AA HF patients.

Functional Outcomes in African-Americans After Robot-Assisted Radical Prostatectomy

Previous studies have demonstrated differences in surgical outcomes after radical prostatectomy based on ethnicity. We compared sexual and urinary outcomes in African-American (AA) patients 6 and 12 months after robot-assisted radical prostatectomy (RARP) with those of non-AA patients. We reviewed our RARP database at our institution for patients with at least 12 months of follow-up. Erectile function was defined using the University of California, Los Angeles Prostate Cancer Index as erections "firm enough for masturbation and foreplay" or "firm enough for intercourse," while urinary continence was defined as being "pad free." Only patients who were potent and pad free preoperatively were included in the analysis. Multivariate logistic regression was used to compare postoperative potency and urinary pad-free status between AA and non-AA patients while controlling for pertinent demographic, clinical, and pathologic variables. In the urinary continence analysis, 140 AA patients and 576 non-AA patients were included, compared with 105 AAs and 500 non-AA patients who were included in the analysis of sexual function. At 12 months postoperatively, a smaller proportion of AA patients were potent compared with non-AA patients (60% vs 76.4%, P=0.001). Similarly, we found a lower incidence of pad-free status for AA patients at 12 months postoperatively (55.7% vs 69.8%, P=0.039). Similar functional results were found at 6 months postoperatively for both analysis groups. AA men appear to have worse urinary and sexual outcomes at 12 months after RARP compared with non-AA patients. At 6 months, there is no statistically significant difference. Further, longer-term studies are needed to validate these results.

Contribution of calcium, phosphorus and 25-hydroxyvitamin D to the excessive severity of secondary hyperparathyroidism in African-Americans with CKD

Parathyroid hormone (PTH) levels in African-American (AA) chronic kidney disease (CKD) patients exceed those in patients of other races; mechanisms are unknown. We performed a cross-sectional analysis of initial laboratory data collected on 2028 CKD patients (505 AA) from US practices using a laboratory CKD service. Serum calcium (Ca), phosphorus (P), 25-hydroxyvitamin D (25-D) and plasma PTH levels were compared between the two groups. Mean PTH for AA exceeded PTH for non-AA in Stages 2-5 (P<0.001, all four stages). 25-D levels were higher for non-AA in Stages 1-3 (P<0.001). Serum Ca and P did not differ between groups at any stage. Full adjustment for these variables using multivariable generalized linear modeling did not remove the effect of AA race: AA PTH values exceeded non-AA values in CKD Stages 2-5 (P<0.02, all four stages). Serum Ca, P and 25-D were all inversely correlated with PTH levels irrespective of race, but all factors combined accounted for ∼42% of the variance in PTH. PTH rises with progressive CKD stage far more in AA than in non-AA patients, and only a moderate component of the rise in PTH is explained by changes in serum Ca, P and 25-D in either group. These findings concur with those from other large CKD cohorts and support the need for further study to determine other factors responsible for this racial difference.

Evidence that abnormally large seasonal declines in vitamin D status may trigger SLE flare in non-African Americans.

Cross-sectional studies have shown that low vitamin D (25-hydroxyvitamin D (25(OH)D)) is associated with increased systemic lupus erythematosus (SLE) activity. This study is the first to assess the temporal relationship between 25(OH)D levels and onset of SLE flare. This assessment was made possible because of the specimen bank and database of the Ohio SLE Study (OSS), a longitudinal study of frequently relapsing SLE that involved regular bimonthly patient follow-up. We identified for this study 82 flares from 46 patients that were separated by at least 8 months from previous flares. Serum 25(OH)D levels were measured at 4 and 2 months before flare, and at the time of flare (a flare interval). We found that for flares occurring during low daylight months (LDM, Oct-Mar), 25(OH)D levels were decreased at the time of flare, but only in non-African American (non-AA) patients (32% decrease at flare, compared to 4 months prior, p < 0.001). To control for seasonal effects, we also measured 25(OH)D levels in the LDM "no-flare" intervals, which were intervals that matched to the same calendar months of the patients' LDM flare intervals, but that didn't end in flare (n = 24). For these matches, a significant decrease occurred in 25(OH)D levels during the flare intervals (18.1% decrease, p < 0.001), but not during the matching no-flare intervals (6.2% decrease, p = 0.411). For flares occurring during high daylight months (HDM), 25(OH)D levels changed only in non-AA patients, increasing slightly (5.6%, p = 0.010). Analysis of flare rates for the entire OSS cohort (n = 201 flares) revealed a tendency for higher flare rates during LDM compared to HDM, but again only in non-AA patients (p = 0.060). Flare rates were lower during HDM for non-AA patients compared to AA patients (p = 0.028). In conclusion, in non-AA SLE patients, unusually large declines in 25(OH)D during LDM may be mechanistically related to SLE flare, whereas relatively high 25(OH)D levels during HDM may protect against flare.