Publications by authors named "Sejong Bae"

130 Publications

Supporting Trainees by Addressing Inappropriate Behaviors by Patients.

South Med J 2021 Feb;114(2):111-115

From the Division of General Internal Medicine and the Division of Preventive Medicine, University of Alabama at Birmingham School of Medicine, Birmingham.

Objectives: Physicians in training may be particularly vulnerable to the negative effects of discrimination and inappropriate behaviors by patients. We sought to determine the frequency of inappropriate behaviors by patients toward Internal Medicine (IM) residents, residents' confidence to manage the behaviors, and differences among demographic characteristics, including race, sex, and level of clinical experience.

Methods: We developed a curricular session to equip IM residents and faculty to respond to discrimination or inappropriate behaviors by patients. Before the session, we surveyed residents about their experiences with macroaggressions, microaggressions, and other inappropriate behaviors using a 16-question survey instrument. We used descriptive statistics to summarize the participants' characteristics and the χ or Fisher exact test for comparison between groups.

Results: Eighty-two percent (27 of 33) of residents who attended the workshop completed the survey. We found that the majority of residents experienced patient macro- and microaggressions. More than 50% had a personal experience or witnessed experience with a macroaggression related to race (56%) or gender (59%). Seventy percent of residents personally experienced a microaggression by a patient. Women and residents of color are more likely to experience these types of encounters, which become more common in residents with higher postgraduate year level. Confidence in how to appropriately respond to such encounters is low.

Conclusions: Our study highlights that macro- and microaggressions by patients toward IM residents are common. Curricula are needed to equip trainees with tools to appropriately respond during such encounters.
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http://dx.doi.org/10.14423/SMJ.0000000000001205DOI Listing
February 2021

Cancer-related Beliefs and Preventive Health Practices among Residents of Rural vs. Urban Counties in Alabama.

Cancer Prev Res (Phila) 2021 Feb 1. Epub 2021 Feb 1.

Nutrition Sciences, University of Alabama at Birmingham

Cancer incidence and mortality are higher in the U.S. Deep South, likely due to increased tobacco-use, obesity, poor diet, and physical inactivity. This study explores whether cancer-related beliefs and lifestyle practices differ by rural-urban status or other socio-demographic factors in a random sample of 855 residents across Alabama.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0458DOI Listing
February 2021

Dietary table grape protects against UV photodamage in humans: 2. molecular biomarker studies.

J Am Acad Dermatol 2021 Jan 20. Epub 2021 Jan 20.

Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.01.036DOI Listing
January 2021

Dietary table grape protects against UV photodamage in humans: 1. clinical evaluation.

J Am Acad Dermatol 2021 Jan 20. Epub 2021 Jan 20.

Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.01.035DOI Listing
January 2021

Differences Related to Cancer Screening by Minority and Rural/Urban Status in the Deep South: Population-based Survey Results.

J Cancer 2021 1;12(2):474-481. Epub 2021 Jan 1.

O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham (UAB), Birmingham, AL.

Cancer mortality in the U.S. Deep South exceeds national levels. A cross-sectional survey was undertaken across Alabama to discern cancer beliefs and screening practices, and compare data from racial/ethnic minority versus majority and rural versus urban respondents. Using population-based methods, we approached 5,633 Alabamians (ages 50-80) to complete a 58-item survey (administered in-person, via telephone, or the web). Descriptive statistics were used to summarize findings; two-tailed, chi-square and t-tests (α<0.05) were used to compare minority-majority and rural-urban subgroups. The response rate was 15.2%; respondents identified as minority (n=356) or majority (n=486), and rural (n=671) or urban (n=183). Mean (SD) age was 63.7 (10.2) and >90% indicated stable housing, and healthcare coverage and access. Rural and minority versus urban and majority respondents were significantly more likely to have lower education, employment, and income, respectively. Most respondents equated cancer as a "death sentence" and were unable to identify the age at which cancer screening should begin. Few rural-urban subgroup differences were noted, though significant differences were observed between minority versus majority subgroups for mammography (36.7% versus 49.6%, p<.001) and colorectal cancer screening (34.5% vs. 47.9%, <0.001). Furthermore, while minorities were significantly more likely to report ever having a colonoscopy (82.1% versus 76.1%, =0.041) and to have received fecal occult blood testing within the past year (17.2% versus 12.2%, =0.046), routine adherence to screening was <20% across all subgroups. Cancer early detection education is needed across Alabama to improve cancer screening, and particularly needed among racial/ethnic minorities to raise cancer awareness.
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http://dx.doi.org/10.7150/jca.49676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738985PMC
January 2021

Expression of trefoil factor 3 is decreased in colorectal cancer.

Oncol Rep 2021 Jan 30;45(1):254-264. Epub 2020 Oct 30.

Center for Clinical and Translational Science (CCTS), University of Mississippi School of Pharmacy (UMSOP) and University of Mississippi Medical Center, Jackson, MS 39216, USA.

In colorectal cancer (CRC), high expression of trefoil factor 3 (TFF3) is associated with tumor progression and reduced patient survival; however, bioinformatics analyses of public 'omics' databases show low TFF3 expression in CRCs as compared to normal tissues. Thus, we examined TFF3 expression in CRCs and matching normal tissues to evaluate its role in CRC progression. TFF3 gene expression was characterized using the bioinformatics portal UALCAN (http://ualcan.path.uab.edu). Tissue microarrays (TMAs) of archival CRC specimens (n=96) were immunostained with anti‑human TFF3 antibodies. Immunohistochemical (IHC) staining intensity was semi‑quantitatively scored. For this cohort, the median follow‑up was 5.4 years. Associations between clinical and pathological variables were determined using Chi‑square or Fisher's exact tests. Univariate disease‑free survival was estimated by the Kaplan‑Meier method. Omics data analyses by UALCAN showed downregulation of TFF3 expression in CRC relative to normal tissue at protein (χ2, P<0.0001) levels. There was a similar decreasing trend of TFF3 expression in the pathologic stages of the CRCs (RNA, χ2, P=0.88 and protein, χ2 P<0.0001). UALCAN data analysis showed that TFF3 exhibited 27% lower mRNA expression in tumors with mutant TP53 (P=0.007). Confirming the findings of omics analyses, IHC analysis of TMAs exhibited lower TFF3 expression in 95.6% (65 of 68) of the available normal‑tumor matching pairs (χ2, P<0.0001). There was no statistically significant association of tumor TFF3 expression with patient sex, race/ethnicity, tumor location within the colorectum, Tumor, Node, Metastasis (TNM) stage, lymph node metastasis, or surgical margins. However, low TFF3 IHC staining in tumor tissue was associated with histological grade (P=0.026). Kaplan‑Meier survival analysis showed no prognostic value of low TFF3 expression relative to those with high expression (log‑rank, P=0.605). Our findings demonstrate low expression of TFF3 in CRCs. Association between low TFF3 and histopathological features suggests involvement of this molecule in progression of CRC.
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http://dx.doi.org/10.3892/or.2020.7829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716703PMC
January 2021

The bio-sonographic index. A novel modality for early detection of acute kidney injury after complex vascular surgery. A protocol for an exploratory prospective study.

PLoS One 2020 17;15(11):e0241782. Epub 2020 Nov 17.

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

Objective: Acute kidney injury (AKI) is a common complication of complex aortic surgery with high mortality, morbidity and health care expense. The current definition of AKI does not allow for structural characterization of the kidneys and utilizes functional indices with substantial limitations leading to delayed diagnosis and ineffective interventions. The aim of this study is to develop a method of early detection of structural renal abnormalities that can precede and predict the occurrence of AKI in this population. We propose a novel combined index of ultrasonography (shear wave elastography), biomarkers of renal stress (urinary insulin growth factor binding protein-7, IGFBP-7 and inhibitor of tissue metalloproteinase-2, TIMP-2) and renal injury markers (urinary neutrophil gelatinase-associated lipocalin -NGAL)- the bio-sonographic index (BSI).

Methods: A prospective observational study at a tertiary referral center will be performed enrolling 80 patients undergoing elective open and endovascular repair of the visceral aorta. The BSI will be evaluated at baseline, and at 6 and 24 hours after the procedure. The primary outcome is the occurrence of AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Each patient will be his/her own control. A reference group of 15 healthy volunteers who are not undergoing interventions will be enrolled to test the feasibility of and to refine the novel SWE protocol. The BSI will be tested for its predictability of the occurrence of AKI. Comparisons will be made between individual and combined components of the BSI and traditional markers used in the KDIGO definition; serum creatinine and urine output in terms of baseline status of the kidney. Correlations will be made between the BSI and conventional indices of AKI and exploratory analyses will be conducted to identify individual disease patterns using the BSI.

Discussion: We hypothesize that the BSI will be a sensitive index of early structural abnormalities that precede and predict the occurrence of AKI as defined by KDIGO in complex vascular surgery.

Trial Registration: ClinicalTrials.gov NCT04144894. Registered 1/6/2020.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241782PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671487PMC
January 2021

Assignment of opsonic values to pneumococcal reference serum 007sp and a second pneumococcal OPA calibration serum panel (Ewha QC sera panel B) for 11 serotypes.

Vaccine 2020 12 6;38(51):8145-8153. Epub 2020 Nov 6.

Department of Pediatrics, Ewha Womans University College of Medicine, Seoul, Republic of Korea; Center for Vaccine Evaluation and Study, Ewha Womans University College of Medicine, Seoul, Republic of Korea. Electronic address:

Pneumococcal conjugate vaccines (PCVs) have been effective in reducing the disease burden caused by Streptococcus pneumoniae. The first licensed PCV (PCV7) was composed of capsular polysaccharides from seven serotypes. This was followed by PCV10, then PCV13, and currently there are a number of higher valency vaccines in development. As part of licensure, new vaccine iterations require assessment of immunogenicity. Since some antibodies can be non-functional, measuring functional antibodies is desirable. To meet this need, opsonophagocytic assays (OPAs) have been developed. Previous studies have shown there can be significant variations in OPA results from different laboratories. We have previously shown that standardizing OPA data using reference serum 007sp can decrease this variation. To extend this approach to additional serotypes, a panel of sera was tested by five laboratories using a multiplexed OPA for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F. Each sample was tested in five runs with 007sp tested three times in each run. Results were analyzed using a mixed effects ANOVA model. Standardization of the results significantly decreased the inter-laboratory variation for some serotypes. For serotypes 2, 8, and 11A, the variability was reduced by 40%, 45%, and 40%, respectively. For serotypes 12F, 17F, and 20B, the reductions were more modest (14%, 19%, and 24%, respectively). Standardization had little effect for the remaining serotypes. In many cases, the impact of normalization was blunted by the results from five sera that were collected after an extended post-vaccination interval. We have previously reported consensus values for 007sp for 13 serotypes, as well as the creation of a calibration serum panel ("Ewha Panel A"). Here, we report consensus values for 11 additional serotypes for 007sp and the creation of a second serum panel ("Ewha Panel B"). These consensus values will facilitate the development of next-generation PCVs.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704772PMC
December 2020

Less Toxic Chemotherapy in Locally Advanced Breast Cancer.

South Med J 2020 11;113(11):559-563

From the Division of Hematology/Oncology, the Department of Radiation Oncology, the Department of Surgery, the Division of Preventive Medicine, and the UAB Comprehensive Cancer, University of Alabama at Birmingham, Birmingham.

Objectives: Preoperative chemotherapy produces tumor shrinkage in most patients with locally advanced breast cancer, including some pathological complete responses (pCRs). We attempted this using a much less toxic sequential regimen, given with concurrent bevacizumab.

Methods: Patients with locally advanced breast cancer received 3 intravenous doses each of preoperative sequential liposome encapsulated doxorubicin 25 mg/m, paclitaxel 175 mg/m, and cyclophosphamide 600 mg/m, with concurrent bevacizumab every 2 weeks without growth factor support.

Results: Between March 2008 and December 2009, 32 patients received treatment. There was no cardiotoxicity, and other toxicity was mild (no grade 4 or 5 toxicity). No long-term toxicity, including cardiotoxicity, has been observed. Every patient had ≥30% reduction in tumor size; 9 of 31 patients who completed chemotherapy had pCR at operation. Seven years later, 22 of 32 patients remain free of recurrence and 27 of 32 are alive.

Conclusions: The preoperative chemotherapy used appears to be comparably effective, but much less toxic than that used in most conventional regimens and should be studied further. Concurrent treatment with bevacizumab (reported separately) did not provide any additional benefit.
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http://dx.doi.org/10.14423/SMJ.0000000000001169DOI Listing
November 2020

Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk.

J Am Coll Cardiol 2020 09;76(13):1507-1516

Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.

Objectives: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.

Methods: This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.

Results: During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).

Conclusions: Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.
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http://dx.doi.org/10.1016/j.jacc.2020.07.059DOI Listing
September 2020

Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer.

Cells 2020 08 27;9(9). Epub 2020 Aug 27.

Department of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.

An abnormality in hedgehog (Hh) signaling has been implicated in the progression of prostate cancer (PCa) to a more aggressive and therapy-resistant disease. Our assessments of human PCa tissues have shown an overexpression of the Hh pathway molecules, glioma-associated oncogene homolog 1 (GLI-1), and sonic hedgehog (SHH). The effect of the natural compound thymoquinone (TQ) in controlling the expression of Hh signaling molecules in PCa was investigated in this study. We generated planetary ball-milled nanoparticles (PBM-NPs) made with a natural polysaccharide, containing TQ, and coated with an RNA aptamer, A10, which binds to prostate-specific membrane antigen (PSMA). We prepared docetaxel-resistant C4-2B-R and LNCaP-R cells with a high expression of Hh, showing the integration of drug resistance and Hh signaling. Compared to free TQ, A10-TQ-PBM-NPs were more effective in controlling the Hh pathway. Our findings reveal an effective treatment strategy to inhibit the Hh signaling pathway, thereby suppressing PCa progression.
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http://dx.doi.org/10.3390/cells9091976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563377PMC
August 2020

A batch-effect adjusted Simon's two-stage design for cancer vaccine clinical studies.

Biometrics 2020 Aug 21. Epub 2020 Aug 21.

O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.

In the development of cancer treatment vaccines, phase II clinical studies are conducted to examine the efficacy of a vaccine in order to screen out vaccines with minimal activity. Immune responses are commonly used as the primary endpoint for assessing vaccine efficacy. With respect to study design, Simon's two-stage design is a popular format for phase II cancer clinical studies because of its simplicity and ethical considerations. Nonetheless, it is not straightforward to apply Simon's two-stage design to cancer vaccine studies when performing immune assays in batches, as outcomes from multiple patients may be correlated with each other in the presence of batch effects. This violates the independence assumption of Simon's two-stage design. In this paper, we numerically explore the impact of batch effects on Simon's two-stage design, propose a batch-effect adjusted Simon's two-stage design, demonstrate the proposed design by both a simulation study and a therapeutic human papillomavirus vaccine trial, and briefly introduce a software that implements the proposed design.
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http://dx.doi.org/10.1111/biom.13358DOI Listing
August 2020

Biological and Clinical Significance of the CCR5/CCL5 Axis in Hepatocellular Carcinoma.

Cancers (Basel) 2020 Apr 5;12(4). Epub 2020 Apr 5.

Department of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.

Despite the improvement in survival for patients with liver cancer (LCa) in recent decades, only one in five patients survive for 5 years after diagnosis. Thus, there is an urgent need to find new treatment options to improve patient survival. For various cancers, including LCa, the chemokine CCL5 (RANTES) facilitates tumor progression and metastasis. Since the function of the CCR5/CCL5 interaction in LCa cell proliferation and migration is poorly understood, the present study was undertaken to investigate the role of the CCR5/CCL5 axis in these processes. Flow cytometry, RT-PCR, Western blot, and immunofluorescence techniques were used to quantify the expression of CCR5 and CCL5 in LCa cells. To determine the biological significance of CCR5 expressed by LCa cell lines, a tissue microarray of LCas stained for CCR5 and CCL5 was analyzed. The results showed higher expression ( < 0.001) of CCR5 and CCL5 in hepatocellular carcinoma (HCC) tissues compared to non-neoplastic liver tissues. Furthermore, to delineate the role of the CCR5/CCL5 interaction in LCa cell proliferation and migration, various LCa cells were treated with maraviroc, a CCR5 antagonist, in the presence of CCL5. These data demonstrated the biological and clinical significance of the CCR5/CCL5 axis in LCa progression. The targeting of this axis is a promising avenue for the treatment of LCa.
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http://dx.doi.org/10.3390/cancers12040883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226629PMC
April 2020

A CD24-p53 axis contributes to African American prostate cancer disparities.

Prostate 2020 05 13;80(8):609-618. Epub 2020 Mar 13.

Department of Genetics and O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer.

Methods: Samples of formalin-fixed, paraffin-embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53 and TP53 .

Results: CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r = .308, P < .001) and MDM2 (r = .227, P = .004). There was a negative correlation for CD24 with ARF (r = -.280, P < .001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P = .004) but not for mutant p53 (AA/EA: 28% vs 21%; P = .152). In 32 CD24 /mutant p53 cases, a TP53 mutation was found in five cases, but no TP53 mutation was found.

Conclusion: The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities.
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http://dx.doi.org/10.1002/pros.23973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176538PMC
May 2020

Associations of social, physical, and financial factors with diet quality among older, community-dwelling women.

Menopause 2020 07;27(7):756-762

Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Objective: This analysis examined whether specific social, physical, and financial factors were associated with diet quality among older, community-dwelling women.

Methods: This cross-sectional analysis was conducted in a subset of 6,094 community-dwelling Women's Health Initiative participants who completed a food frequency questionnaire, administered from 2012 to 2013, and a self-administered supplemental questionnaire, administered approximately 1 year later. The supplemental questionnaire included five questions assessing social, physical, and financial factors related to eating. Diet quality was assessed with the Healthy Eating Index-2010 (HEI-2010; range of 0-100; higher score indicates a higher quality diet). The total HEI-2010 score was calculated by summing individual scores representing the intake of nine adequacy components (beneficial food groups) and three moderation components (food groups to limit). Associations of responses to the five questions on the supplemental questionnaire with HEI-2010 scores were examined with multiple linear regression, adjusting for relevant covariates.

Results: Mean ± standard deviation age of participants was 78.8 ± 6.7 years. Reporting eating fewer than two meals per day, having dental or other mouth problems causing problems with eating, and not always being able to shop, cook, or feed oneself were associated with statistically significantly lower HEI-2010 scores, compared with those not reporting these issues, after multivariable adjustment: 5.37, 2.98, and 2.39 lower scores, respectively (all P values <0.0001). Reporting eating alone most of the time and not always having enough money to buy food were not associated with HEI-2010 scores.

Conclusions: Among older, community-dwelling women, eating fewer than two meals per day, dental and other mouth problems, and diminished ability to shop for food, prepare meals, and feed oneself were associated with lower diet quality. These are potential targets for interventions to improve diet quality in older women. : Video Summary:http://links.lww.com/MENO/A561.
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http://dx.doi.org/10.1097/GME.0000000000001528DOI Listing
July 2020

Perioperative outcomes of laparoscopic, robotic, and open approaches to pheochromocytoma.

J Robot Surg 2020 Dec 28;14(6):849-854. Epub 2020 Feb 28.

Department of Urology, University of Alabama at Birmingham, Faculty Office Tower 1107, 510 20th Street South, Birmingham, AL, 35233, USA.

While multiple studies have demonstrated that minimally invasive surgical (MIS) techniques are a safe and efficacious approach to adrenalectomy for pheochromocytomas (PC), these studies have only been small comparative studies. The aim of this multi-institutional study is to compare perioperative outcomes between open and MIS, stratified by robotic and conventional laparoscopic, techniques in the surgical management of PC. We retrospectively evaluated patients who underwent adrenalectomy for PCs from 2000 to 2017 at three different institutions. Clinical, perioperative, and pathologic parameters were analyzed using t test, Chi square, and Fisher exact statistical measures. Of the 156 adrenalectomy cases performed, 26 (16.7%) were with an open approach and 130 (83.3%) using MIS techniques. Of the MIS procedures, 41 (31.5%) were performed robotically and 89 (68.5%) performed laparoscopically without robotic assistance. Demographic and clinical parameters were similar between the open and MIS groups. Patients, who underwent MIS procedure had a lower complication rate (p = 0.04), shorter hospitalization (p = 0.02), shorter operative time (p < 0.001), and less blood loss (p = 0.002) than those who underwent open surgical resection. Conventional laparoscopic and robotic operative approaches resulted in similar complication rates, length of hospitalization, and blood loss. Our study is one of the largest cohorts comparing the perioperative outcomes between conventional laparoscopic and robotic adrenalectomies in patients with PC. Our results support that MIS techniques have potentially lower morbidity compared to open techniques, while laparoscopic and robotic approaches have similar perioperative outcomes.
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http://dx.doi.org/10.1007/s11701-020-01056-9DOI Listing
December 2020

14-3-3 proteins protect AMPK-phosphorylated ten-eleven translocation-2 (TET2) from PP2A-mediated dephosphorylation.

J Biol Chem 2020 02 3;295(6):1754-1766. Epub 2020 Jan 3.

Department of Urology, University of Alabama, Birmingham, Alabama 35294

Ten-eleven translocation-2 (TET2) is a member of the methylcytosine dioxygenase family of enzymes and has been implicated in cancer and aging because of its role as a global epigenetic modifier. TET2 has a large N-terminal domain and a catalytic C-terminal region. Previous reports have demonstrated that the TET2 catalytic domain remains active independently of the N-terminal domain. As such, the function of the N terminus of this large protein remains poorly characterized. Here, using yeast two-hybrid screening, co-immunoprecipitation, and several biochemical assays, we found that several isoforms of the 14-3-3 family of proteins bind TET2. 14-3-3 proteins bound TET2 when it was phosphorylated at Ser-99. In particular, we observed that AMP-activated protein kinase-mediated phosphorylation at Ser-99 promotes TET2 stability and increases global DNA 5-hydroxymethylcytosine levels. The interaction of 14-3-3 proteins with TET2 protected the Ser-99 phosphorylation, and disruption of this interaction both reduced TET2 phosphorylation and decreased TET2 stability. Furthermore, we noted that protein phosphatase 2A can interact with TET2 and dephosphorylate Ser-99. Collectively, these results provide detailed insights into the role of the TET2 N-terminal domain in TET2 regulation. Moreover, they reveal the dynamic nature of TET2 protein regulation that could have therapeutic implications for disease states resulting from reduced TET2 levels or activity.
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http://dx.doi.org/10.1074/jbc.RA119.011089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008385PMC
February 2020

Correction to: Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma.

J Immunother Cancer 2019 Oct 22;7(1):273. Epub 2019 Oct 22.

Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA.

Following publication of the original article [1], the author reported that the current funding section "Kidney Cancer Association Young Investigator Grant provided funding for this project" should be replaced with "Kidney Cancer Association Young Investigator Grant and Bucks County Board provided funding for this project."
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http://dx.doi.org/10.1186/s40425-019-0735-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806554PMC
October 2019

Evaluation of MSKCC Preprostatectomy nomogram in men who undergo MRI-targeted prostate biopsy prior to radical prostatectomy.

Urol Oncol 2019 12 5;37(12):970-975. Epub 2019 Sep 5.

Department of Urology, University of Alabama at Birmingham, Birmingham, AL; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL.

Introduction: The Memorial Sloan Kettering Cancer Center (MSKCC) Preprostatectomy nomogram is a widely used resource that integrates clinical factors to predict the likelihood of adverse pathology at radical prostatectomy. Adoption of magnetic resonance imaging targeted biopsy (TB) permits optimized detection of clinically-significant cancer over systematic biopsy (SB) alone. We aim to evaluate the prognostic utility of the MSKCC Preprostatectomy nomogram with TB pathology results.

Methods: Men who underwent SB and magnetic resonance imaging TB who later underwent radical prostatectomy at our institution were included. Patient information was entered into the MSKCC Preprostatectomy nomogram using 5 biopsy reporting schemes with TB reported by both individual core (IC) and aggregate group (AG) methods. The likelihood of extraprostatic extension, seminal vesicle invasion, and lymph node involvement as predicted by the nomogram for each biopsy reporting schema were compared to radical prostatectomy pathology.

Results: We identified 63 men from January 2014 to November 2017. On receiver operating characteristic analysis, IC-TB, AG-TB, SB plus IC-TB, and SB plus AG-TB exhibited similar, if not improved, area under the curve compared to SB alone in predicting extraprostatic extension (0.671, 0.674, 0.658, and 0.6613 vs. 0.6085). This was similarly observed for seminal vesicle invasion prediction using SB plus IC-TB compared to SB alone (0.727 vs. 0.733). For lymph node involvement, superior but nonsignificant area under the curve was observed for AG-TB (0.647) compared to IC-TB (0.571) and SB alone (0.524) CONCLUSIONS: Using TB pathology results either alone or combined with SB pathology results as input to the MSKCC Preprostatectomy nomogram appears comparable for prognosticating adverse pathology on radical prostatectomy compared to SB alone, but robust validation is warranted prior to adoption into clinical practice.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.006DOI Listing
December 2019

Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma.

J Immunother Cancer 2019 05 28;7(1):139. Epub 2019 May 28.

Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA.

Background: The tumor immune microenvironment has become the focus of research in clear cell renal cell carcinoma (ccRCC) due to its important role in immune surveillance post nephrectomy. This study investigates the correlation of tumor infiltrating immune cell characteristics with rates of recurrence following surgery in localized ccRCC.

Methods: We morphologically identified and scored tumor infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) stained slides of patients with localized ccRCC (stage ≥T1b excluding stage IV). The University of Alabama at Birmingham (UAB) dataset (n = 159) was used to discover and the Fox Chase Cancer Center (FCCC) dataset (n = 198) was used to validate the results of morphologic immune cell analysis. We then performed gene expression analysis using the Immune Profile panel by NanoString in the UAB cohort and identified immune cells and pathways associated with recurrence, followed by validation in the Cancer Genome Atlas (TCGA) ccRCC dataset. Infiltrating immune cell types were identified by gene expression deconvolution.

Results: The presence of TILs identified by morphology correlated with higher T cell, Th1, CD8+ T and Treg gene signatures. Recurrence was associated with lower T cells and higher neutrophils. Higher Teffector (Teff)/Treg ratio correlated with lower rate of recurrence and was validated in the TCGA dataset. Genes associated with adaptive immune response were downregulated in tumors that recurred. Unsupervised hierarchical clustering identified a subset of patients with over-expression of adaptive response genes including CD8, CD3, GZMA/B, PRF1, IDO1, CTLA4, PDL1, ICOS and TIGIT. These patients had higher morphologic lymphocyte infiltration and T cell gene expression. Higher levels of TILs identified by morphology correlated with higher rates of recurrence in our discovery dataset but not in our validation set.

Conclusions: Recurrence of ccRCC following surgery was associated with lower T cell infiltrate, lower adaptive immune response and higher neutrophil gene expression. Presence of higher Teff/Treg ratio correlated with lower recurrence.
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http://dx.doi.org/10.1186/s40425-019-0621-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540413PMC
May 2019

Race-associated expression of MHC class I polypeptide-related sequence A (MICA) in prostate cancer.

Exp Mol Pathol 2019 06 17;108:173-182. Epub 2019 Apr 17.

Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA; Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA; Center for Clinical and Translational Science (CCTS), University of Mississippi School of Pharmacy & University of Mississippi Medical Center, Jackson, MS, USA. Electronic address:

Despite the lack of a complete understanding of the disparities involved, prostate cancer (PCa) has both higher incidence and death rates in African American Men (AAM) relative to those of Caucasian American Men (CAM). MHC class I polypeptide related sequence A (MICA) is an innate immunity protein involved in tumor immunoevasion. Due to a lack of reports of race-specific expression of MICA in PCa, we evaluated MICA expression in patients' tumors and in cell lines from a racially diverse origin. Immunohistochemistry was done on a tissue microarray (TMA) with antibodies against MICA. Tumor MICA mRNA was assessed by data mining using Oncomine and PROGeneV2. Surface MICA and release rate of soluble (s) MICA was evaluated in PCa cell lines originally derived from African American (MDA-PCa-2b) or Caucasian (LNCaP and DU-145) PCa patients. Prostate tumor tissue had a 1.7-fold higher MICA expression relative to normal tissue (p < .0001). MICA immunoreactivity in PCa tissue from AAM was 24% lower (p = .002) compared to CAM. Survival analysis revealed a marginal association of low MICA with poor overall survival (OS) (p = .058). By data mining analysis, a 2.9-fold higher level of MICA mRNA was evidenced in tumor compared to normal tissue (p < .0001). Tumors from AAM had 24% lower levels of MICA mRNA compared to tumors from CAM (p = .038), and poor prognosis was found for patients with lower MICA mRNA (p = .028). By flow cytometry analysis, cell fraction positive for surface MICA was of 3% in MDA-PCa-2b cells, 54% in DU-145 cells, and 67% in LNCaP cells (p < .0001). sMICA was detected in DU-145 and LNCaP cells, but was not detected in MDA-PCa-2b cells. Both LNCaP and DU-145 cells were sensitive to cytolysis mediated by Natural killer (NK) cells. MDA-PCa-2b cells, however were between 1.3-fold at 10:1 Effector:Target (E:T) ratio (p < .0001) and 2-fold at 50:1 E:T ratio (p < .0001) more resistant to NK-mediated cytolysis relative to cells from Caucasian origin. These results suggest that MICA expression may be related to the aggressive nature of PCa. Our findings also demonstrate for the first time that there are variations in MICA expression in the context of racial differences. This study establishes a rationale for further investigation of MICA as a potential race-specific prognostic marker in PCa.
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http://dx.doi.org/10.1016/j.yexmp.2019.04.010DOI Listing
June 2019

Prostate cancer cells hyper-activate CXCR6 signaling by cleaving CXCL16 to overcome effect of docetaxel.

Cancer Lett 2019 07 8;454:1-13. Epub 2019 Apr 8.

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, 30310, USA; Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA, 30310, USA. Electronic address:

Molecular reprogramming in response to chemotherapeutics leads to poor therapeutic outcomes for prostate cancer (PCa). In this study, we demonstrated that CXCR6-CXCL16 axis promotes DTX resistance and acts as a counter-defense mechanism. After CXCR6 activation, cell death in response to DTX was inhibited, and blocking of CXCR6 potentiated DTX cytotoxicity. Moreover, in response to DTX, PCa cells expressed higher CXCR6, CXCL16, and ADAM-10. Furthermore, ADAM-10-mediated release of CXCL16 hyper-activated CXCR6 signaling in response to DTX. Activation of CXCR6 resulted in increased GSK-3β, NF-κB, ERK1/2 phosphorylation, and survivin expression, which reduce DTX response. Finally, treatment of PCa cells with anti-CXCR6 monoclonal antibody synergistically or additively induced cell death with ∼1.5-4.5 fold reduction in the effective concentration of DTX. In sum, our data imply that co-targeting of CXCR6 would lead to therapeutic enhancement of DTX, leading to better clinical outcomes for PCa patients.
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http://dx.doi.org/10.1016/j.canlet.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748218PMC
July 2019

Nonparametric estimation of risk tracking indices for longitudinal studies.

Stat Methods Med Res 2020 02 4;29(2):481-497. Epub 2019 Apr 4.

Department of Preventive Medicine, Northwestern Feinberg School of Medicine, Chicago, IL, USA.

Tracking a subject's risk factors or health status over time is an important objective in long-term epidemiological studies with repeated measurements. An important issue of time-trend tracking is to define appropriate statistical indices to quantitatively measure the tracking abilities of the targeted risk factors or health status over time. We present a number of local and global statistical tracking indices based on the rank-tracking probabilities, which are derived from the conditional distribution functions, and propose a class of kernel-based nonparametric estimation methods. Confidence intervals for the estimators of the tracking indices are constructed through a resampling subject bootstrap procedure. We demonstrate the application of the tracking indices using the body mass index and systolic blood pressure data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Statistical properties of the estimation methods and bootstrap inference are investigated through a simulation study and an asymptotic development.
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http://dx.doi.org/10.1177/0962280219839427DOI Listing
February 2020

Racial and Ethnic Differences in Obesity in People With Spinal Cord Injury: The Effects of Disadvantaged Neighborhood.

Arch Phys Med Rehabil 2019 09 25;100(9):1599-1606. Epub 2019 Mar 25.

Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, the United States. Electronic address:

Objective: To examine the role of neighborhood in the relation between race and obesity in people with spinal cord injury (SCI).

Design: A cross-sectional analysis of survey data from National SCI Database linked with neighborhood data from American Community Survey by census tract.

Setting: A total of 17 SCI Model Systems centers.

Participants: Individuals (N=3385; 2251 non-Hispanic whites, 760 non-Hispanic blacks, 374 Hispanics) who completed a follow-up assessment during 2006-2017 (mean duration of injury, 8.3±9.9y) and resided in 2934 census tracts.

Intervention: Not applicable.

Main Outcome Measures: Body mass index (BMI) (kg/m).

Results: The overall prevalence of obesity was 52.9% (BMI≥25.0) and 23.3% (BMI≥30.0). Hispanics were 67.0% more likely to be obese (BMI≥30.0 kg/m) relative to non-Hispanic whites (odds ratio, 1.67; 95% confidence interval, 1.27-2.18), after controlling for demographic and injury-related characteristics. Most of the non-Hispanic blacks (66.8%) were living in neighborhoods with high concentrated disadvantaged index (CDI), compared to 35.0% of Hispanics and 9.2% of non-Hispanic whites living in this similar neighborhood status (P<.0001). After accounting for CDI, the odds of being obese in Hispanics decreased (odds ratio, 1.51; 95% confidence interval, 1.15-1.99). Regardless of race and ethnicity, people with SCI from disadvantaged neighborhoods were 42.0%-70.0% more likely to be obese than those from minimal CDI neighborhoods.

Conclusions: Neighborhood characteristics partially diminish racial differences in obesity. Weight management for the SCI population should target those who are Hispanic and living in the disadvantaged neighborhoods.
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http://dx.doi.org/10.1016/j.apmr.2019.02.008DOI Listing
September 2019

CC chemokines are differentially expressed in Breast Cancer and are associated with disparity in overall survival.

Sci Rep 2019 03 8;9(1):4014. Epub 2019 Mar 8.

Department of Microbiology, Biochemistry and Immunology; Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA, 30310, USA.

Despite recent advances, breast cancer (BrCa) still affects many women and the impact is disproportional in African Americans (AA) compared to European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting contribution of biological differences in BrCa disparity. Our laboratory was first to show involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner and KMplotter, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, -7, -11, -17, -20, -22 and -25 in BrCa tissues. High mRNA levels of CCL7, -8, -17, -20 and -25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, -7, -8, -17, -20 and -25 was highest in TNBC. Expression of CCL11 and CCL22 was associated with HER2. CCL7, -8, -17, -20 and -25 were elevated in AAs. In conclusion, our analysis suggests significant association of CC-chemokines in BrCa progression, OS and disparate disease outcome in AA compared to EA patients.
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http://dx.doi.org/10.1038/s41598-019-40514-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408438PMC
March 2019

Higher CXCL16 exodomain is associated with aggressive ovarian cancer and promotes the disease by CXCR6 activation and MMP modulation.

Sci Rep 2019 02 21;9(1):2527. Epub 2019 Feb 21.

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.

Ovarian cancer (OvCa) is the leading cause of death from gynecological malignancies. Five-year survival rate of OvCa ranges from 30-92%, depending on the spread of disease at diagnosis. Role of chemokines is well appreciated in cancer, including OvCa. However, their precise role is understudied. Here, we show clinical and biological significance of CXCR6-CXCL16 and ADAM10 in OvCa. Expression of CXCR6 and N-terminal CXCL16 was significantly higher in serous carcinoma tissues compared to endometrioid. OvCa cells (SKOV-3 and OVCAR-3) also showed higher expression of CXCR6 than normal ovarian epithelial cells (IOSE-7576) while CXCL16 was higher in SKOV-3 than IOSE-7576. Furthermore, N-terminal CXCL16 was higher in conditioned media of OvCa cells than IOSE-7576. Compared to OVCAR-3, SKOV-3 cells, which had higher CXCL16, expressed significantly higher transcripts of ADAM10, a protease that cleaves CXCL16. OVCAR-3 cells showed higher CXCR6 specific migration whereas SKOV-3 cells showed more invasion. Difference in invasive potential of these cells was due to modulation of different MMPs after CXCL16 stimulation. Higher CXCR6 expression in serous papillary carcinoma tissues suggests its association with aggressive OvCa. Increased migration-invasion towards CXCL16 implies its role in metastatic spread. Therefore, CXCR6-CXCL16 axis could be used to differentiate between aggressive versus non-aggressive disease and as a target for better prognosis.
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http://dx.doi.org/10.1038/s41598-019-38766-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385302PMC
February 2019

Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC.

Cancer Res 2019 04 7;79(7):1413-1425. Epub 2019 Feb 7.

Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.

Although c-MYC and mTOR are frequently activated proteins in prostate cancer, any interaction between the two is largely untested. Here, we characterize the functional cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling during tumor progression. Deletion of in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells. Conversely, inhibition of mTOR increased pT58 but decreased pS62. Loss of both FOXP3 and TSC1 in prostate cancer cells synergistically enhanced c-MYC expression via regulation of c- transcription and protein phosphorylation. This crosstalk between FOXP3 and TSC1 appeared to be mediated by both the mTOR-4EBP1-c-MYC and FOXP3-c-MYC pathways. In mice, and double deletions in the prostate led to prostate carcinomas at an early age; this did not occur in these mice with an added c- deletion. In addition, we observed synergistic antitumor effects of cotreating mice with inhibitors of mTOR and c-MYC in prostate cancer cells and in and double-mutant mice. In human prostate cancer, loss of nuclear FOXP3 is often accompanied by low expression of TSC1. Because loss of FOXP3 transcriptionally induces c- expression and loss of TSC1 activates mTOR signaling, these data suggest cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling that converges on c-MYC to regulate tumor progression. Coadministration of c-MYC and mTOR inhibitors may overcome the resistance to mTOR inhibition commonly observed in prostate cancer cells. SIGNIFICANCE: These results establish the principle of a synergistic action of TSC1 and FOXP3 during prostate cancer progression and provide new therapeutic targets for patients who have prostate cancer with two signaling defects. http://cancerres.aacrjournals.org/content/canres/79/7/1413/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445690PMC
April 2019

Psoas Muscle Density in Combination with Model for End-Stage Liver Disease Score Can Improve Survival Predictability in Transjugular Intrahepatic Portosystemic Shunts.

J Vasc Interv Radiol 2019 02;30(2):154-161

Department of Medicine, University of Alabama at Birmingham, Birmingham, D619 19th Street South, AL 35249; Department of Radiology, University of Alabama at Birmingham, Birmingham, D619 19th Street South, AL 35249. Electronic address:

Purpose: To examine the role of psoas muscle density (PD) measurement before transjugular intrahepatic portosystemic shunt (TIPS) creation in predicting survival when combined with Model for End-stage Liver Disease (MELD) score.

Materials And Methods: The medical records of 241 patients with cirrhosis who underwent TIPS creation between June 2005 and June 2015 were retrospectively reviewed. The patients were divided into 2 groups: those with variceal bleeding (VB; n = 113) and those with volume overload (VO; n = 128). The study included 149 men (62%), and mean patient age was 56 years ± 9.6 (range 24-83). Mean MELD score before TIPS creation was 11.8 ± 5.7. A threshold sensitivity of pre-TIPS PD for the assessment of mortality was calculated and then correlated with survival after TIPS creation. Receiver operating characteristic curves comparing 12-month mortality were used to assess the improvement in survival predictability after TIPS creation when the PD threshold was combined with MELD score vs MELD score alone.

Results: Mean post-TIPS follow-up was 29.9 month ± 34.1 (range 1-3700 days). There was no significant difference in 3- or 12-month mortality rates between the VB and VO groups (32.7% vs 25.8% [P = .23] and 46% vs 46.1% [P = .99], respectively). The MELD score threshold for prediction of survival was 15 (P < .0001). There was no difference in the mean PD between VB and VO groups (34.2 HU ± 8.8 and 33.1 HU ± 10.3, respectively; P = .359). The increase in MELD score after TIPS creation was significant in both groups (VB, P = .0013; VO, P < .0001). The threshold of pre-TIPS PD for discrimination of survival was 29.4 HU (P < .0001), and PD measurements greater than this threshold were associated with a lower risk of mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P = .0006). Compared with the use of MELD score alone, the addition of PD measurement significantly increased the area under the curve from 0.61 to 0.68 (P = .0006).

Conclusions: Measurement of PD improved overall survival predictability in patients with cirrhosis undergoing TIPS creation when used in conjunction with MELD score. The best survival outcome was observed in patients with MELD score < 15 in combination with PD > 29.4 HU.
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http://dx.doi.org/10.1016/j.jvir.2018.10.006DOI Listing
February 2019

Racial and Geographic Disparities in Hepatocellular Carcinoma Outcomes.

Am J Prev Med 2018 11;55(5 Suppl 1):S40-S48

Emergency Department, University of Alabama at Birmingham, Birmingham, Alabama.

Introduction: Hepatocellular carcinoma disproportionately affects minorities. Southern states have high proportions of black populations and prevalence of known risk factors. Further research is needed to understand the role of southern geography in hepatocellular carcinoma disparities. This paper examined racial disparities in hepatocellular carcinoma incidence, demographics, tumor characteristics, receipt of treatment, and all-cause mortality in southern and non-southern cancer registries.

Methods: Surveillance Epidemiology and End Results data were probed in 2015 to identify 43,868 patients diagnosed with hepatocellular carcinoma from 2000 to 2012 (5,455 in southern registries [Atlanta, Louisiana, and Rural and Greater Georgia]).

Results: Southern registries showed steeper increases of age-adjusted hepatocellular carcinoma incidence (from 2.89 to 5.29cases/100,000 people) versus non-southern areas (from 3.58 to 5.54cases/100,000 people). Blacks were over-concentrated in southern registries (32% vs 10%). Compared with whites, blacks were significantly younger at diagnosis, more likely diagnosed with metastasis, and less likely to receive surgical therapies in both registry groups. After adjustment, blacks had a significantly higher risk of all-cause mortality compared with whites in southern (hazard ratio=1.10, p=0.007) and non-southern areas (hazard ratio=1.08, p<0.001). For overall populations, southern registries had higher risk of all-cause mortality versus non-southern registries (hazard ratio=1.13, p<0.001).

Conclusions: Age-adjusted incidence rates of hepatocellular carcinoma are plateauing overall, but are still rising in southern areas. Race and geography had independent associations with all-cause mortality excess risk among patients with hepatocellular carcinoma. Further studies are needed to understand the root causes of potential mortality risk excess among overall populations with hepatocellular carcinoma living in the South.

Supplement Information: This article is part of a supplement entitled African American Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health.
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http://dx.doi.org/10.1016/j.amepre.2018.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708601PMC
November 2018