Racial Disparity in HCV Demographics and Treatment Between Interferon Era (2002-2003) and Direct Acting Anti-viral Era (2019).

Introduction  Direct-acting antiviral (DAA) treatment increased the sustained viral response (SVR) rate of patients with the hepatitis C virus (HCV) and eliminated response disparities between African American (AA) and non-AA patients seen with interferon (IFN). The aim of this study was to compare 2019 HCV patients (DAA era) to patients from January 1, 2002 and December 31, 2003 (IFN era) in our predominantly AA clinic population. Methods We extracted data on 585 HCV patients seen in 2019 (DAA era) and compared them to 402 patients seen in the IFN era. Results Most HCV patients were born between 1945 and 1965, but in the DAA era more younger patients were identified. Non-AA patients in both eras were less likely to be infected with genotype 1 compared to AA (95% vs 54%, P<0.001). Fibrosis was not increased in the DAA Era as compared to the IFN era as assessed either by serum-based assays (APRI, FIB-4) or transient elastography (FibroScan) (DAA era) vs biopsy (IFN era). More patients were treated in 2019 compared to 2002-2003 (159/585=27% vs 5/402=1%). For untreated patients, subsequent treatment within one year of the initial visit was low and similar in both eras (35%). Conclusion There continues to be a need to screen patients born between 1945 and 1965 for HCV as well as to identify increasing numbers of patients below this age cohort. Even though current therapies are oral, highly effective, and can be 8-12 weeks in duration, significant numbers of patients were not treated within a year of first visit.

From sneaker to bourgeois male: Long-term observations on recognized tompot blenny Parablennius gattorugine individuals reveal new information on their biology.

The behaviour of the tompot blenny Parablennius gattorugine was studied by underwater observation and photography on the south-west coast of the UK over an 11 year period, with >50 individuals identified at two locations by their distinctive skin markings. Observations showed males engaging in rapid swimming behaviour when approached by a female, and younger males using alternative 'sneaker' tactics before becoming 'bourgeois' territory-holders. The noninvasive recognition technique also facilitated detailed observations on territory retention (up to 7 years) and agonistic behaviours among both males and females.

Celiac Disease Patients With Coronary Artery Disease: A Nationwide Population-Based Study.

Background Coronary artery disease (CAD) is associated with celiac disease (CD) with limited evidence. However, the common risk factors linking CD and CAD are still lacking in the literature. Known CAD risk factors include hypertension, hyperlipidemia, type 2 diabetes, obesity, and tobacco use. Common risk factors linking CD and CAD are poorly documented. Objective There are three objectives: Firstly, to evaluate potential demographic differences between CD patients with CAD and without CAD. Secondly, to analyze the risk factors of CAD in CD patients. Lastly, to compare CD-CAD and matched non-CD CAD to determine whether there are additional CAD risks in individuals with CD. Methods The study is a nationwide retrospective case-control study. The National Inpatient Sample (NIS) database was used to identify patients admitted between 2016 and 2018 with a principal or secondary diagnosis of CD. We analyzed sociodemographic and clinical risk factors of CAD in CD patients and compared the CD-CAD population with the matched non-CD CAD cohort. Results Out of 23,441 hospitalizations with CD in 2016-2018, 4244 (18%) were found to have CAD. Established CAD risk factors identified in CD patients included hypertension, hyperlipidemia, type 2 diabetes, and a family history of CAD. In contrast, tobacco use is not a CAD risk factor in CD patients. Female patients with CD had 55% lesser odds of CAD than male patients. The odds of CAD in CD patients with hyperlipidemia were five times higher, 1.2 times higher with essential hypertension, and two times higher with type 2 diabetes. Patients with CAD had a higher prevalence of iron deficiency anemia (9.33% CD-CAD and 8.28% non-CAD CD Vs. 7.32% non-CD CAD). Conclusions Our study confirms that, as with non-CD individuals, males and the White race are at increased CAD risk in the CD population. CD-CAD patients have a higher hyperlipidemia prevalence than non-CD CAD patients. CD patients with type 1 diabetes have an early diagnosis of CAD compared to CD patients with type 2 diabetes. Iron deficiency anemia is a statistically significant risk factor for CAD in CD patients.

Role of Bowel Preparation in Adenoma Detection Rate and Follow-up Recommendations in African American Dominant Patient Population.

INTRODUCTION: Bowel preparation quality in colonoscopy is one of the most essential components of quality assessment. According to the latest guidelines, inadequate bowel preparation warrants repeat colonoscopy in less than a year. Our aim was to investigate the role of bowel preparation in adenoma detection rate (ADR), its relationship with patients' demographics, and compliance with subsequent surveillance recommendations with guidelines. METHODS: This is a retrospective chart review study. Bowel preparation quality was divided into three categories: high, intermediate, and low. ADR and polyp detection rates (PDR) were calculated as the number of patients with adenoma or polyp divided by the total number of patients. RESULTS: Among 1,062 patients (934 African American and 128 non-African American) 81%, 11%, and 8% had high, intermediate, and low-quality bowel preparations, respectively. Race, gender, age, type of endoscopist, and body mass index did not play any role in bowel preparation quality. ADR and PDR were significantly higher in African Americans as compared to non-African Americans. ADR was significantly lower in the low-quality as compared to the high- and intermediate-quality bowel preparations (OR=2.13; p=0.0032). Bowel preparation quality was not correlated with subsequent follow-up recommendations. Academic gastroenterologists and surgeons had the highest and lowest compliance with surveillance guidelines, respectively. CONCLUSIONS: Racial and gender disparity appears to have no meaningful effect on the quality of bowel preparation. Only two categories (adequate [high/intermediate] or inadequate [low-quality]) may be used for follow-up recommendations. Non-compliance with surveillance guidelines is concerning and may inadvertently increase the interval risk of colorectal cancer.

Evaluating the Improvement in Colonoscopy Quality Indicators Subsequent to Publication of Professional Society Guidelines.

Introduction  Quality metrics of colonoscopy should be routinely monitored with a focus on optimizing the patient's subsequent risk of colorectal cancer development. Documentation of bowel preparation, adenoma detection rate (ADR), and post-colonoscopy follow-up recommendations are three of the most important quality indicators for colonoscopy, but significant improvement has been challenging to achieve. The goal of this study is to determine whether the publication of colonoscopy quality indicator guidelines in 2015 resulted in an improvement in quality measures of physicians in our endoscopy suite as compared to before. Methods  We reviewed the electronic medical records of patients who underwent a screening or surveillance colonoscopy in 2014 and 2017. Colonoscopies were performed in an open-access medical center endoscopy suite, staffed by three groups of physicians (academic gastroenterologists (AGs), non-academic gastroenterologists (non-AGs), and surgeons). We gathered demographic data, bowel preparation reports, follow-up recommendations, and notice to patient's primary care physician, and calculated ADR for patients. Age- and gender-matched patients in both years were analyzed for ADR. These data were further subcategorized for each group of physicians. Results  There were 553 patients in 2014 and 1,095 in 2017. Overall, male gender and African American race constituted the majority of patients in both years. Among age- and gender-matched patients in 2014 and 2017 (412 and 243 patients, respectively), ADR within each group of endoscopists was not significantly different between these two years (AGs 44% vs. 50%; non-AGs 32% vs. 27%; surgeons 25% vs. 21%; p>0.05 for all). However, in 2014 and 2017, ADR was significantly higher in the AG group as compared to the non-AG group and surgeons (p<0.006 and p<0.0004, respectively). Reporting of bowel preparation quality (82% vs. 87%) and documenting the recommended period for follow-up surveillance colonoscopy in the report (68% vs. 78%) improved between 2014 and 2017 (p=0.002 and p=0.0001, respectively). Correct recommendations for follow-up surveillance colonoscopy only improved significantly in the AG group (74% in 2014 as compared with 82% in 2017, p=0.003). Conclusion  Based on the current guidelines, AG physicians are far exceeding the target ADR goals, and are superior compared to other groups of endoscopists. Although improvements were noted after guideline publications, areas of needed improvement with respect to meeting gastroenterology society guidelines for quality remained. The fact that individual physicians are performing and billing in an endoscopy suite staffed and equipped by a medical center creates an environment where responsibility for improvement in quality cannot be readily assigned.

Racial Diversity in Hepatocellular Carcinoma in a Predominately African-American Population at an Urban Medical Center.

PURPOSE: Surveillance, treatment, and outcomes for African-American (AA) populations with hepatocellular carcinoma (HCC) remain under evaluated. This study evaluated demographics, surveillance, therapy, and outcomes for a predominately AA population. METHODS: The electronic medical records of a large health-care provider were used to identify 274 patients with visits for HCC between 2010 and 2017. Tumor size at diagnosis was defined by imaging with ≤ 5 cm being defined as "small." Surveillance for HCC was defined based on ultrasound (US) assessments. RESULTS: Patients were primarily AA (78%) and male (76%) with an average age at diagnosis of 62 years. Hepatitis C virus (HCV) was more likely to be a risk factor for the development of HCC in AA as compared to non-AA (92% vs 67%; p < 0.005). Surveillance rates were low (16% for AA vs 7% for non-AA). An aspartate aminotransferase platelet ratio index (APRI) value > 0.7 within 2 years of tumor diagnosis was a strong predictor for the risk of the development of HCC (86% AA vs 79 % non-AA). In this study, race was not a factor in treatment or outcomes, and most patients received tumor ablative treatment. CONCLUSION: Given the low surveillance rates and the demonstrated increased survival for patients with small tumors, ways to increase surveillance must be initiated. The results of this study demonstrate the need for physician/patient education on the importance of surveillance US. Further, this study supports routine assessment of APRI in AA patients in an effort to identify patients in whom intensive surveillance will significantly improve earlier detection of tumors.

Variations in Screening Adenoma Detection Rate by Specialty of Physicians in a Predominately African American Population.

BACKGROUND: Screening colonoscopy aims to interrupt the adenoma-carcinoma sequence by removing all precancerous adenomatous polyps. Adenomatous polyp detection rate (ADR) can vary between endoscopists as well as between race, age, and risk of colorectal cancer (CRC). The purpose of this study was to compare ADR among academic gastroenterologists (A-GI), non-A-GI, and surgeons for endoscopies performed in the same endoscopic suite of a large medical center with a predominately African American (AA) population. METHODS: All screening colonoscopies performed in 2014 for patients aged 62-76 years were identified using the electronic medical records data. Patients with average risk and high risk of CRC defined as having a 'personal history of polyps' or 'family history of CRC', and history of ulcerative colitis and Fecal Occult Blood Test/Fecal Immunochemical Test (FOBT/FIT) positivity were included. Patients with incomplete colonoscopy (defined as failing to achieve cecal intubation or poor preparation) and unrecovered tissue biopsy were excluded. ADR was calculated for three groups of endoscopists: A-GIs, non-A-GIs, and surgeons. RESULTS: A total of 573 screening colonoscopies was analyzed. The endoscopists comprised five A-GIs, eight non-A-GIs, and six surgeons. The majority of patients were of AA decent (71%), female (54%) with an average age of 66 years. Patients classified as average risk comprised 79% of the population. Most of the colonoscopies were performed by A-GI (n=339), followed by non-A-GI (n=144), and surgeons (n=90). The ADR for A-GI was 50% as compared to 32% for non-A-GI (p<0.001) and 25% for surgeons (p<0.001). Also, A-GI were more likely to identify ≥3 adenomas during screening colonoscopies. Significant differences were observed (p<0.001) in the mean time of colonoscopy for A-GI (30 mins) non-A-G (14 mins), and surgeons (18 mins). CONCLUSION: Significant variation in the ADR between endoscopists belonging to different specialties were observed. Although all appear to achieve acceptable ADR (ie at least 25 for men and 15 for women), academic gastroenterologists had better performance than non-academic GI and surgeons. This may be explained by a significantly longer average duration of procedures for the highest ADR group.

Performance characteristics of EUS-FNA biopsy for adrenal lesions: A meta-analysis.

BACKGROUND AND OBJECTIVE: The role of EUS-FNA biopsy (EUS-FNAB) for detection of metastatic lesions (mets) to adrenals has not been evaluated systematically. Our aim is to systematically evaluate the performance characteristics of EUS-FNAB in detecting metastasis to the adrenal glands. MATERIALS AND METHODS: We performed a systematic search on PubMed and OvidSP from January 1990 to July 2016 using various search terms for EUS and adrenal lesion. Only articles published in English literature were included in the study. Studies with fewer than 10 patients were excluded from the study. Publication bias was assessed using Begg-Mazumdar test and visual inspection of funnel plots. RESULTS: Eight studies including 360 adrenal lesions that underwent EUS-FNAB were identified. Of these, 137 FNABs were conclusive for malignancy. Sensitivity of EUS-FNAB in detecting metastasis to the adrenals was 95% (95% confidence interval [CI]: 90%-98%) and specificity was 99% (95% CI: 96%-100%). Pooled positivity of EUS-FNAB in detecting lung cancer metastasis to the adrenals was 44% (95% CI: 31.5%-57.3%). No evidence of publication bias was noted. CONCLUSION: Our study demonstrates that EUS-FNAB is highly sensitive and specific in detecting metastasis to adrenals. It also shows that up to about half of the patients with lung cancer and adrenal lesions on imaging have metastasis, a finding with profound implications on lung cancer staging and treatment.

A case of acute liver failure due to carfilzomib in multiple myeloma.

WHAT IS KNOWN AND STUDY OBJECTIVE: Carfilzomib is a newer drug approved for the treatment of relapsing and refractory multiple myeloma. It has been rarely associated with acute liver failure (ALF). CASE SUMMARY: We present a case of 58-year-old man presenting with abnormal liver function tests and subsequently diagnosed with ALF due to carfilzomib. Liver enzymes improved significantly after discontinuation of the drug. WHAT IS NEW AND CONCLUSION: Even though ALF due to carfilzomib has been documented rarely in clinical studies, no detailed case report has been published so far. Patients on carfilzomib should be monitored for ALF, and prompt discontinuation of drug is necessary in such cases.

Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C.

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

Overestimate of Fibrosis by FIBROSpect® II in African Americans Complicates the Management of their Chronic Hepatitis C.

BACKGROUND: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). AIMS: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. METHODS: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. RESULTS: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. CONCLUSIONS: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams: a mixed-methods approach.

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice.

Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

Effect of Treatment for CHC on Liver Disease Progression and Hepatocellular Carcinoma Development in African Americans.

BACKGROUND AND AIMS: African Americans (AA) historically have a low response rate to hepatitis C therapies, and there is limited information available for this patient population regarding the development and treatment of chronic hepatitis C (CHC). The aim of this study was to evaluate liver disease progression and hepatocellular carcinoma (HCC) development in AA with CHC. METHODS: Between 1995 and 2008, 246 AA patients with CHC were identified from a database of patients and followed until 2012-2013 (average 8 years) or the development of HCC after 2008. RESULTS: Viral clearance (intent to treat; sustained virus response (SVR)) was achieved in 15% of patients with interferon based therapies with or without ribavirin. AA patients who achieved an SVR (n=22) did not develop HCC or new onset cirrhosis, whereas the HCC incidence in untreated AA patients was 23% (51/203). Patients who achieved an SVR also had improved fibrosis, as defined by the AST Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) score, relative to nonresponders and untreated patients. CONCLUSIONS: The severity of liver disease at the first visit (except for cirrhosis) correlated with the development of HCC, but because of the overlap in values between patients, these measurements were not useful for predicting individual risk. Since cirrhosis at the first visit was not a predictive factor, treatment with newer antiviral therapies is the best option for reducing the incidence of advanced liver disease and its harmful outcomes in the AA population.

Intimate Partner Violence in Pakistan: A Systematic Review.

Intimate partner violence (IPV) is a major social and public health problem affecting people in various cultures and societies. Though the issue of IPV in Pakistan has been researched since the 1990 s, no attempt has been made systematically to review the available evidence on IPV in Pakistan. This article presents findings of a systematic review of available empirical literature related to IPV in Pakistan. Using various key words, MEDLINE, CINAHL, and PsycINFO were searched to identify relevant studies. This resulted in the identification of 55 potential studies for inclusion. After application of exclusion criteria 23 studies were identified, 20 of which used quantitative research designs, two used qualitative designs and one adopted a mixed method case study approach. All studies reported men as the perpetrators of IPV and women as its victims. Findings are presented and discussed for IPV for its forms, predictors, effects and victims' responses. Pakistani peoples' perceived reasons for and their attitudes towards IPV are also presented and discussed.

A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma.

OBJECTIVE: IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10 days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, peripheral blood lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2. METHODS: Absolute lymphocyte numbers were determined in whole blood using the TetraONE System. Lymphocytes were further separated on Ficoll-Hypaque gradients and evaluated by multiparameter flow cytometry. Lymphocyte numbers, including regulatory T cells (Treg) and naïve, memory and effector T cells, were compared in pre- and post-therapy specimens. RESULTS: Total lymphocyte numbers remained unchanged after IRX-2 therapy. Significant changes occurred in numbers of circulating B cells and NKT cells, which decreased following IRX-2 therapy. The frequency of circulating Treg (CD4(+)CD25(high)) remained unaltered (e.g., 6.7 ± 0.6% vs. 7.5 ± 0.8%; means ± SEM) as was the CD8(+)/Treg ratio (6.6 before and 6.7 after IRX-2 therapy). The mean absolute number of CD3(+)CD45RA(+)CCR7(+) (naïve) T cells was decreased after IRX-2 therapy but numbers of total memory (i.e., central and peripheral) and terminally differentiated T cells were unchanged. CONCLUSIONS: IRX-2-mediated reductions in B and NKT cell numbers in the blood suggest a redistribution of these cells to tissues. A decrease in naïve T cells implies their up-regulated differentiation to memory T cells. Unchanged Treg numbers after IRX-2 therapy indicate that IRX-2 does not expand this compartment, potentially benefiting anti-tumor immune responses.

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen.

Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

Peptide Based Vaccine Approaches for Cancer-A Novel Approach Using a WT-1 Synthetic Long Peptide and the IRX-2 Immunomodulatory Regimen.

Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors including choice of immunogenic cancer rejection antigens, optimization of vaccine platforms and immune adjuvants to effectively polarize the immune response, and incorporation of strategies to reverse cancer mediated immune suppression by utilization of effective adjuvant/immune modulators. WT-1 (Wilms' tumor gene 1) is a cancer antigen that is required for tumorigenesis, expressed in a high percentage of tumor cells and rarely expressed in adult normal cells. Moreover spontaneous immunity to WT-1 is seen in cancer patients and can be augmented with various therapeutic vaccine approaches. IRX-2 is an immune modulator with demonstrated preclinical and clinical pleiotropic immune activities including enhancement of the immune response to potential tumor antigens. This paper presents the rationale and preclinical data for utilizing the WT-1 tumor antigen in a novel vaccine platform consisting of a synthetic long peptide containing multiple class I and class II epitopes in combination with the IRX-2 immunomodulatory regimen to overcome immuno-suppressive pathways and enhance the anti-tumor response.