Citations

Transplantation of gene-corrected autologous hepatocytes can cure metabolic disease in a preclinical pig model of hereditary tyrosinemia type 1.

Abstract Background: African immigrants in the US have substantially higher prevalences of viral hepatitis and hepatocellular carcinoma than the general population. In Minnesota, which has the third largest state population of African immigrants in the US, the incidence and mortality for hepatocellular carcinoma among Blacks is 3 times higher than Caucasians (The 2012 Minnesota Department of Health Cancer Report). Most African immigrants are unaware of their risk for hepatocellular carcinoma which contributes to substantial liver health disparities. Limited research exists on the burden of viral hepatitis and hepatocellular carcinoma among African immigrants. Thus, we conducted a pilot study to evaluate the knowledge, attitudes, and behaviors (KAB) of African immigrants related to liver disease. Methods: The study used a community-engaged research framework. The research team consisted of stakeholders from an academic medical center and Ethiopian, Liberian, and Kenyan community-based organizations and faith-based centers. A semi-structured focus group guide was developed using a KAB approach with open-ended questions. Content analysis was used to thematically code the transcribed data. Qualitative analysis software (ATLAS.TI) was used to organize codes and highlight major themes contributing to liver health disparities. Results: We enrolled 63 participants and conducted 9 focus groups (1 in Amharic, 2 in Oromo, and 6 in English) in Rochester and Minneapolis, Minnesota. The mean age was 47±19; 32 participants (51%) were male; the median years lived in the US was 12 years. General knowledge of the modes of transmission of viral hepatitis and of the prevention and development of liver cancer was minimal. Themes related to barriers to viral hepatitis screening and vaccination included perceived cultural stigma and use of traditional remedies. Common sources of general health information included internet, pamphlets, friends, family, spiritual leaders and healthcare professionals. Healthcare professionals are the source for information on screening, prevention, transmission and treatment of viral hepatitis and liver cancer. Most participants sought healthcare at reputable medical institutions. Media sources and community-based events at faith-centers were preferred modes of information dissemination on viral hepatitis and liver cancer screening and prevention. Conclusions: Participants identified several factors contributing to the increased burden of hepatocellular carcinoma in Minnesota including lack of knowledge of disease transmission and progression, cultural stigma/taboos, and lack of preventive care. Culturally and linguistically appropriate interventions are needed to increase awareness, prevention, early detection, and treatment of viral hepatitis and liver cancer among African immigrants in Minnesota. Citation Format: Essa A. Mohamed, Nasra H. Giama, Hassan M. Shaleh, Linda M. Kerandi, Abdul M. Oseini, Hager F. Ahmed Mohammed, Henry M. Kerandi, Dekermue Togbah, Abdiwahab O. Ali, Ibrahim A. Waaeys, Hamdi A. Ali, Safra A. Mohamed, Hawa M. Ali, Joyce E. Balls-Berry, Lewis R. Roberts. Evaluating knowledge, attitudes, and behaviors about viral hepatitis and hepatocellular carcinoma among recent African immigrants in Minnesota: A community-engaged qualitative study. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C01.

Abstract Background: The rising incidence of hepatocellular carcinoma in the US is partly due to increased immigration from sub-Saharan Africa. Viral hepatitis is prevalent in sub-Saharan Africa, resulting in ~20% of all hepatocellular carcinoma cases worldwide. Community-based education and screening efforts aimed at identifying viral hepatitis cases among African immigrants will likely reduce the burden of hepatocellular carcinoma. Aim: To determine the knowledge, attitudes and behaviors (KAB) of Liberian and Kenyan immigrants residing in Minnesota about hepatitis B virus and hepatitis C virus screening, vaccination, acquisition, and disease management. Methods: A community-engaged research framework was used for the development of this cross-sectional study. The team created a survey using validated items designed to assess the KAB of viral hepatitis measured on a 1 to 20 scale with 1 being low and 20 being high. Using community-engaged methodology, participants who were ≥18 years of age and self-identified either as Liberian and Kenyan were recruited from churches, community centers, and community events. The survey was administered between June 2014 and February 2015. Spearman's rho correlation was used to identify associations among scores while the Mann-Whitney U-test was used for comparisons between Liberians and Kenyans. Results: Of 80 distributed surveys, 73 were returned, achieving a response rate of 91%. Respondents were 50 (64%) Liberians and 23 (29%) Kenyans; 42 (54%) were female; the mean age was 42 years (range 18-90); most were college educated (57%) and had health insurance (83%). 55% reported previous screening for hepatitis B, 51% had completed hepatitis B vaccination and 38% reported being screened for hepatitis C. Mean scores ± SD were 4.6±2.8 for knowledge, 4.7±1.0 for attitude, and 4.2±1.9 for behavior, resulting in poor knowledge and adequate attitude and behavioral levels. Significant and positive linear correlation was observed between attitude and behavior (r=.385, p<.001), while there were no significant correlations between knowledge and attitude (r=-.115, p=.33) or knowledge and behavior (r=-.11, p=.36). When Liberians and Kenyans were compared, knowledge was higher in Liberians (6.2±1.9 vs1.5±1.0; p<.001); there were no significant differences observed in attitude or behavior scores (p>.05 for both). Conclusions: There is lack of awareness among African immigrants of the health risks associated with viral hepatitis which contributes to disparities in healthcare seeking behaviors. It is important to implement comprehensive education and screening programs on viral hepatitis in these communities in order to reduce the burden of viral hepatitis and hepatocellular carcinoma development. Citation Format: Hassan M. Shaleh, Nasra H. Giama, Essa A. Mohamed, Hager F. Ahmed Mohammed, Linda M. Kerandi, Abdul M. Oseini, Abdiwahab O. Ali, Ibrahim A. Waaeys, Jonggi Choi, Henry M. Kerandi, Safra A. Mohamed, Hamdi A. Ali, Hawa M. Ali, Joyce E. Balls-Berry, Lewis R. Roberts. A cross-sectional assessment of knowledge, attitudes, and behaviors about viral hepatitis and hepatocellular carcinoma among Kenyan and Liberian immigrants living in Minnesota. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A46.

OBJECTIVE The etiology of intraneural ganglion cysts has been controversial. In recent years, substantial evidence has been presented to support the articular (synovial) theory for their pathogenesis. The authors sought to 1) perform a systematic review of the world's literature on intraneural cysts, and 2) reinterpret available published MR images in articles by other authors to identify unrecognized joint connections. METHODS In Part 1, all cases were analyzed for demographic data, duration of symptoms, the presence of a history of trauma, whether electromyography or nerve conduction studies were performed, the type of imaging, surgical treatment, presence of a joint connection, intraneural cyst recurrence, and postoperative imaging. Two univariate analyses were completed: 1) to compare the proportion of intraneural ganglion cyst publications per decade and 2) to assess the number of recurrences from 1914 to 2003 compared with the years 2004–2015. Three multivariate regression models were used to identify risk factors for intraneural cyst recurrence. In Part 2, the authors analyzed all available published MR images and obtained MR images from selected cases in which joint connections were not identified by the original authors, specifically looking for unrecognized joint connections. Two univariate analyses were done: 1) to determine a possible association between the identification of a joint connection and obtaining an MRI and 2) to assess the number of joint connections reported from 1914 to 2003 compared with 2004 to 2015. RESULTS In Part 1, 417 articles (645 patients) were selected for analysis. Joint connections were identified in 313 intraneural cysts (48%). Both intraneural ganglion cyst cases and cyst recurrences were more frequently reported since 2004 (statistically significant difference for both). There was a statistically significant association between cyst recurrence and percutaneous aspiration as well as failure to disconnect the articular branch or address the joint. In Part 2, the authors identified 43 examples of joint connections that initially went unrecognized: 27 based on their retrospective MR image reinterpretation of published cases and 16 of 16 cases from their sampling of original MR images from published cases. Overall, joint connections were more commonly found in patients who received an MRI examination and were more frequently reported during the years 2004 to 2015 (statistically significant difference for both). CONCLUSIONS This comprehensive review of the world's literature and the MR images further supports the articular (synovial) theory and provides baseline data for future investigators.

Dual-energy computed tomography (DECT) has recently been suggested as the imaging modality of choice for kidney stones due to its ability to provide information on stone composition. Standard postprocessing of the dual-energy images accurately identifies uric acid stones, but not other types. Cystine stones can be identified from DECT images when analyzed with advanced postprocessing. This case report describes clinical implications of accurate diagnosis of cystine stones using DECT.

Abstract A genome-wide association study (GWAS) of pancreatic cancer conducted within the NCI Cohort Consortium (PanScan I and II) identified pancreatic cancer susceptibility loci on chromosomes 1q32.1/NR5A2, 5p15.33/CLPTM1L/TERT, 9q34.2/ABO, and 13q22.1. The most significant single-nucleotide polymorphism (SNP) identified on 13q22.1, rs9543325, lies in a ~600 kb gene desert; the nearest genes are KLF5, KLF12, PIBF1, DIS3, and BORA (265–586 kb away). Imputation using the 1000 Genomes and DCEG reference datasets did not improve the GWAS signal, but produced a set of highly correlated SNPs for functional follow-up. We performed eQTL analysis to test for association between the genotypes of these functional candidate variants and expression of nearby genes. Among 64 normal derived pancreatic tissue samples, DIS3 expression showed the strongest association with a 30 bp indel variant in the risk locus (P = 4.8 × 10-4), indicating risk alleles associate with reduced DIS3 expression. Mutations in DIS3 have previously been identified in acute myeloid leukemia and multiple myeloma, and its expression has been correlated with metastatic potential in colorectal cancer, suggesting DIS3 is relevant to cancer biology. Chromosome conformation capture identified a physical interaction between the indel-containing locus and a region near the DIS3 promoter. Luciferase assay for regulatory function of this indel-containing locus revealed allele-specific silencer activity for the insertion allele. Supershift electromobility shift assay (EMSA) demonstrated binding of LEF1 specifically to the insertion allele of the indel, which contains two in silico predicted LEF1 binding elements. Finally, through immunohistochemical analysis, high DIS3 protein levels associated with better survival for pancreatic cancer patients (hazard ratio = 2.87, 95% CI = 1.49–5.53, P = 0.001). Our results suggest that at least one target gene for the pancreatic cancer risk variants on chr13q22.1 may be DIS3, and that the underlying biology may be mediated by the novel indel through a long-range repressive effect on DIS3 expression. Citation Format: Jason W. Hoskins, Abdisamad Ibrahim, Mickey Emmanuel, Sarah Manmiller, Jinping Jia, Hemang Parikh, Irene Collins, Kris Ylaya, Sean F. Altekruse, Stephen M. Hewitt, Gloria M. Petersen, Laufey T. Amundadottir. Functional analysis of the chr13q22.1 pancreatic cancer risk locus suggests allele-specific effects on DIS3 expression with prognostic implications. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-09.

Tyrosine kinase inhibitors (TKI) are the initial treatment for majority of newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase (CP) and are associated with marked improvement in hematological, cytogenetic, molecular response and survival rates compared with other therapies. In this review, we summarize the evidence of TKI efficacy for patients with newly diagnosed CP‐CML. Six trials at low risk of bias evaluating TKIs as an initial treatment in adults with newly diagnosed CP‐CML and enrolling 2,456 patients were included. Follow‐up times ranged from a median of 3 months to 5 years. Direct comparison showed statistically higher rates of major molecular response (MMR ≤ 0.1%IS) achievement with second‐generation TKIs at 12 months which was sustained throughout treatment period. Bayesian mixed‐treatment comparison (MTC) analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy. Nilotinib was associated with higher deeper molecular responses (MR4.5 ≤ 0.0032%IS) at 60 months than dasatinib but no difference in MMR. The differences between nilotinib and dasatinib are likely clinically trivial. Among TKIs, nilotinib was found to have the best survival profile. Both nilotinib and dasatinib are associated with significantly better MMR compared to imatinib that is sustained over 60 months. This analysis shows that new‐generation TKIs are not only showing faster response but also maintaining a more potent one through longer follow‐up period. It is important to note out that MTC is not a substitute for well‐conducted RCTs investigating direct comparisons.