tbuckley/cabot-search huggingface dataset:
Abstract P126: Comparing Cardiovascular Risk Factor Progression Between South Asian Men and Women With Diabetes: A Longitudinal Analysis From the Masala Study
Authors: Manasi Deshpandey, Chiung-Yu Huang, Namratha Kandula, Alka M Kanaya
Journal: Circulation (2020)

Introduction: South Asians have a high incidence of type 2 diabetes(DM) and cardiovascular disease (CVD). Women with DM may have greater CVD risk compared to men with DM and women without DM. No study has determined whether the incidence or progression of coronary artery calcium (CAC) score, a measure of atherosclerosis burden, differs between South Asian men and women with DM. Hypothesis: We hypothesize that CAC progression is greater in women with DM as compared to men with DM and women without DM. Methods: We used the data from the MASALA study, a community-based prospective cohort of South Asians from 2 clinical sites without CVD at baseline. We conducted a longitudinal analysis of diabetic participants who were reassessed after 5 years and compared with those without diabetes. We classified incident CAC as any CAC at exam 2 in a participant who had no CAC at baseline. To examine the progression of CVD risk factors over time, we compared change in CAC score, waist circumference, systolic and diastolic blood pressure, HbA1c and lipid levels amongst the diabetic and non-diabetic population by sex. We conducted multivariable linear regression models stratified by diabetes status to determine whether sex was independently associated with change in CAC score and other CVD risk factors. Results: Of 749 participants who were seen in follow-up, 176 (23%) had diabetes at baseline, 65% were men, and mean age was 58 years. Approximately 64% women with DM vs. 28% men with DM had CAC=0, and men had higher median CAC score (49 (IQR 0-247) vs. 0 (IQR 0-46, p&lt;0.001). After mean follow-up of 4.8±0.8 years, incident CAC did not differ between men and women with diabetes (p=0.85). Progression of CAC was greater in men with DM (94, IQR 13-290) compared to women with DM (0, IQR 0-30) (p &lt;0.001). Baseline statin and aspirin use was lower in women with DM (statins: 37% in women vs. 56% in men, p&lt;0.001; aspirin 16% in women vs. 43% in men, p&lt;0.001). In multivariable models, the fold-change in CAC in women (0.22, 95% CI 0.10 - 0.47) was lower than in men (4.54, 95% CI 2.08 - 9.89) and comparable to women without DM (0.30 95%CI 0.21 -0.43), after adjusting for age, baseline CAC, systolic and diastolic blood pressure, total and LDL cholesterol, duration of diabetes, smoking and any medication use (statin, diabetes, or hypertension med). Sex was not associated with change in any CVD risk factor among those with diabetes; but women without DM had greater change in total and LDL cholesterol and waist circumference than men without DM. Conclusion: In this South Asian population, change in CAC score was lower in women with DM than in men with DM, and was comparable to women without DM. These results suggest among South Asians with DM, overall CVD risk may be greater in men than in women.Continued follow-up of the MASALA cohort will determine whether there are sex differences in CVD outcomes.
Diagnostic workup of acute leukemias of ambiguous lineage
Authors: Sanjay S. Patel, Olga K. Weinberg
Journal: American Journal of Hematology (2020)

Acute leukemias of ambiguous lineage (ALAL) comprise acute undifferentiated leukemias (AUL) and mixed-phenotype acute leukemias (MPAL). In the revised fourth edition of the World Health Organization (WHO) classification provided further refinements to the diagnostic criteria for ALAL. Molecular characterization of MPALs using comprehensive next-generation sequencing (NGS) has provided insights into their underlying biology and enabled a deeper understanding of ALAL classification. This review addresses the various components of pathologic assessment to establish a diagnosis of ALAL, and to further subclassify individual cases as AUL or MPAL, with an emphasis on the most up-to-date revisions to diagnostic criteria. In addition, key issues related to the detection of minimal residual disease (MRD) in ALALs and MPALs, and recently uncovered novel molecular diagnostic findings that may be helpful in better distinguishing various types of MPALs from each other, and from their "non-mixed" phenotypic correlates, are also discussed.
Long-term reduction in asthma morbidity following an asthma self-management programme
Authors: WJ D'Souza, H Te Karu, C Fox, M Harper, T Gemmell, M Ngatuere, K Wickens, J Crane, N Pearce, R Beasley
Journal: European Respiratory Journal (1998)

The adult "credit card" asthma self-management plan has been shown to be an effective and acceptable system for reducing asthma morbidity when introduced as part of a 6 month community-based asthma programme. The aim of the present study was to assess the effectiveness of the credit card plan 2 yrs after the end of the programme. Markers of asthma morbidity and use of medical services were compared during the 12 months before enrolment, and 2 yrs after completing the 6 month asthma programme. Of the 69 participants who originally enroled in the 6 month asthma programme, 58 were surveyed 2 yrs after completion of the programme. These participants showed a significant improvement in all but one of the asthma morbidity measures. The proportion waking most nights with asthma in the previous 12 months decreased from 29 to 9% (p=0.02), emergency visits to a general practitioner decreased from 43 to 16% (p=0.001), hospital emergency department visits with asthma decreased from 19 to 5% (p=0.02) and hospital admissions decreased from 17 to 5% (p=0.04). Only 24% of patients reported that they usually monitored their peak flow rate daily, but this increased to 73% during a "bad" attack of asthma. A long-term reduction in asthma morbidity and requirement for acute medical services can result following the introduction of the adult credit card asthma self-management plan. Adult patients with asthma are most likely to undertake peak flow monitoring preferentially during periods of unstable asthma, rather than routinely during periods of good control.
Abstract MP01: Multiple Social Determinants of Health Disparities Increase the Risk of Diabetes and Mortality in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Joanna B Ringel, April P Carson, Doyle M Cummings, Jessica Pena, Christopher Gamboa, Praful Schroff, Monika M Safford
Journal: Circulation (2020)

Introduction: The Healthy People 2020 initiative proposed that social determinants contribute to disparities in health outcomes. While studies have documented the influence of individual social determinants of health (SDOH) on health outcomes, few studies have examined how the aggregation of multiple SDOH within the same person affect health. Hypothesis: We hypothesized that as the number of individual-level and neighborhood-level SDOH increased, the relative risk of incident diabetes and mortality also increased. Methods: This study included 15,310 black and white adults aged &gt; 45 years at baseline (2003-2007) who did not have prevalent diabetes and who completed the 10 year follow-up exam (2014-2016) or died prior to follow-up in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Exposures included 6 SDOH which have been associated with increased health risks: annual household income &lt;$35,000, black race, &lt; high school education, lack of health insurance, residing in a zip code with ≥ 25% poverty, and living in a state with poor public health infrastructure for 10 years prior to 2003. Outcomes were all-cause mortality or incident diabetes, defined as fasting glucose &gt;126 mg/dL, random blood glucose &gt;200 mg/dL, or taking diabetes medication or insulin. Multinomial logistic regression models examined associations of number of SDOH with death and incident diabetes, adjusting for other demographics, health behaviors, and medical conditions. Results: At follow-up, 1,170 (8.7%) had developed diabetes, and 3,790 (26.8%) had died. As the number of SDOH increased, the relative risk of both diabetes and death increased significantly (p for trend &lt;0.001) in both crude and adjusted models (Figure). Conclusions: Counting the aggregate number of SDOH that an individual is exposed to may be a simple way to identify those at greater risk of developing incident diabetes or dying over 10 years. This approach has potential for application in both clinical practice and population health management.
Abstract P293: Work Ability in Adults With Diabetes: A Mixed Methods Study
Authors: Margaret M McCarthy, Allison Vorderstrasse, Joeyee Yan, Angie Portillo, Victoria V Dickson
Journal: Circulation (2020)

Introduction: Over 30 million Americans have a diagnosis of diabetes. The estimated cost of diagnosed diabetes in 2012 was $245 billion, including $69 billion in reduced productivity. Although many adults with diabetes are productive members of the workforce, loss of work productivity has been associated with the presence of diabetes. Hypothesis: We tested the hypothesis that work-related factors were associated with work ability in a sample of working adults with diabetes. Methods: This was a cross-sectional mixed methods descriptive design used to study a national convenience sample of 101 working adults with diabetes. Subjects were recruited through the online tool ResearchMatch, and completed surveys using the secure web application REDCap. Valid surveys assessed job content, work-life balance, work limitations and work ability, followed by qualitative telephone interviews in a sub-sample of 30 adults. Adjusting for hemoglobin A1c and diabetes duration, factors significant in the bivariate statistics were included in the stepwise logistic regression with the outcome of excellent work ability. Lastly, quantitative and qualitative data were integrated for analysis. Results: The sample was 65% female with mean age 54.1±10.5. The majority were White (74%), non-Hispanic (93%), married (51%), worked full-time (65%) and had type 2 diabetes (87%) with a mean duration of 12.4±9.5 years. Less than half (42%) reported their most recent hemoglobin A1c was &lt;7%. They worked 36±14 hours per week and the majority rated their current work ability as either good (42%) or excellent (33%). Factors associated with work ability included co-worker support (p=.007), work-life balance (p&lt;.0001), skill discretion (p=.02), psychological demands (p=.006), and supervisor support (p=.03). Two factors were independently associated with self-reported excellent work ability: increasing co-worker support improved the odds of excellent work ability (OR: 1.4; 95% CI: 1.04-1.9; p=0.025) and poorer work-life balance decreased the odds or excellent work ability (OR: 0.77; 95% CI: 0.67-0.89; p &lt;.0001). Qualitative: Several themes emerged from the data. Most reported no impact of work on keeping medical appointments or managing diabetes at work, and diabetes management was better during a work day since they were on a schedule. Very few report wellness programs at work, and if they exist (e.g. exercise or weight loss program), most do not engage in them. Data integration: Those who reported an excellent work ability also expressed less stress and more control over their daily routine. Conclusions: The majority of the sample reported good or excellent work ability which was related to less stress and more job control. Workers may benefit from wellness programs that address not only diabetes self-management but also job stress, ways to improve co-worker support, and maintaining optimal work-life balance.
Abstract P180: Low Prevalence of Ideal Cardiovascular Health in Patients With Severe Hypercholesterolemia in a Largely Rural Population
Authors: Nicole A Groth, Catherine P Benziger
Journal: Circulation (2020)

Introduction: The American Heart Association’s ideal cardiovascular health (ICH) score is determined by 3 ideal health factors (normal blood pressure, untreated total cholesterol, and glucose) and 4 ideal health behaviors (non-smoking, normal body mass index, high physical activity, and heart healthy diet). Achieving ICH, defined as meeting 5 of the 7 metrics, decreases risk of cardiovascular disease. Prevalence estimates of ICH in patients with severe hyperlipidemia (SH) living in rural areas are lacking. Hypothesis: We aimed to determine the prevalence of poor, intermediate, and ICH in patients with SH in a large healthcare system (Essentia Health), where over 60% of the population is rural. Methods: The electronic medical record-based SH registry is a cross-sectional cohort study at the Essentia Health of patients who have ever had a low-density lipoprotein - cholesterol value of 190 mg/dL or higher, since 01/01/2000 (n=17,925). Patients were excluded if they did not have a visit at the institution within the past 5 years (n=209) or were outside of the age 20-75 years (n=3,153). Physical activity and healthy diet were not available in the record and were excluded from the score. Patients with missing data were assumed ideal given low clinical suspicion of conditions. Methods: A total of 14,544 (81.1%) of the SH registry patients met inclusion criteria (mean age 63 +13 years; 58.9% female). Figure 1 shows the prevalence of ICH metrics in the total population. Only 3 (0.02%) people met all five of the ideal metrics (score of 10); more females had a score of 8-10 than males (12.5% vs. 9.6%). A total of 13 (0.08%) had a score of 0 (poor) and 3.0% had a score of 0-2 with no sex differences. Not smoking and ideal glucose were the most prevalent health factors. The mean score was 5.6 (+1.6) with no sex differences. Conclusions: There is low prevalence of ICH in patients with SH living in rural populations. The metrics with the lowest prevalence and therefore highest potential for improvement are the health factors: total cholesterol and body mass index.
Utilizing multiparametric flow cytometry in the diagnosis of patients with primary plasma cell leukemia
Authors: Laura A. Evans, Dragan Jevremovic, Bharat Nandakumar, Angela Dispenzieri, Francis K. Buadi, David Dingli, Martha Q. Lacy, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Eli Muchtar, Rahma Warsame, Taxiarchis V. Kourelis, Ronald Go, Stephen Russell, John A. Lust, Yi Lin, Mustaqeem Siddiqui, Robert A. Kyle, Morie A. Gertz, S. Vincent Rajkumar, Shaji K. Kumar, Wilson I. Gonsalves
Journal: American Journal of Hematology (2020)

The diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear, and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of ≥200 cPCs/μL by MFC (N = 25 or 5% of the total population) was chosen to identify patients with ≥5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. For patients with ≥200 cPCs/μL by MFC compared to the remainder of the cohort, the median Time to next therapy (TTNT) was 18 vs 30 months and the median OS was 38 vs 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients.
Abstract 15205: Enhancing Effective Drug Delivery in Cardiac Ischemia Reperfusion Injury With Semipermeable Nanoparticles
Authors: Samuel A Wickline, Katherine James, Jawad Fazal, Carla Weinheimer, Hua Pan
Journal: Circulation (2018)

Introduction: Prevention of cardiac ischemia-reperfusion injury (IRI) can be thwarted by microvascular damage that prevents sufficient access of therapeutic agents. We sought to define the state of...
Is chemotherapy failure a contraindication for liver resection in liver metastases of colorectal cancer? A multivariate analysis
Authors: U. P. Neumann, A. Thelen, S. Jonas, H. Riess, P. Neuhaus
Journal: Journal of Clinical Oncology (2007)

4066 Background: Liver resection is the only curative treatment offering a chance of long-term survival in patients with colorectal liver metastases. Chemotherapy is increasingly proposed as neoadjuvant treatment in patients with irresectable liver metastases. However, a large number of patients show progress while on chemotherapy. Recent data indicated that liver resection in patients receiving chemotherapy with tumor progress is associated with poor outcome. The aim of the study was to identify risk factors for poor outcome in patients with preoperative chemotherapy with resectable colorectal liver metastases (CRM). Methods: We retrospectively analyzed the outcome of 168 consecutive patients who underwent liver resection for CRM after systemic chemotherapy between 1995 and 2004. Overall, 132 (78.6%) patients had first line, 24 (14.3%) patients second line and 12 (7.2%) third or fourth line chemotherapy. Three groups of patients were identified according to the chemotherapy response. 48 patients (28.6%) had a tumor response (group 1), in 20 (11.9%) the condition stabilized (group 2), and 100 (59.5%) patients had tumor progression (group 3). Median follow-up was 1.8 yrs (range (6 days - 9.5 yrs). Results: Demographic data, size of largest node, number of nodes, extent of resection and postoperative course were equally distributed between groups. Overall, survival was 89%, 56%, and 31% at 1, 3, and 5 years, respectively. Five-year survival was similar between groups. In the univariate analysis, only incomplete resection and vascular invasion were associated with poor outcome. In the multivariate analysis, only vascular invasion was significantly associated with fatal outcome. Neither the number of lines nor the chemotherapeutic agent was associated with decreased survival. Conclusions: In a large patient population, liver resection offered long-term survival for patients with multiple colorectal metastases, even in cases with tumor growth whilst receiving chemotherapy. This underlines that, whenever a curative resection is possible, surgical resection of liver metastases is justified even in patients with therapy failure due to chemotherapy. No significant financial relationships to disclose.
Abstract 01: Retinal Microvascular Signs and White Matter MRI Findings: The Atherosclerosis Risk in Communities Neurocognitive Study
Authors: Jennifer A Deal, Melinda C Power, Karen Bandeen-Roche, Michael Griswold, David Knopman, Thomas Mosley, Keenan Walker, Rebecca F Gottesman, A. Richey Sharrett
Journal: Circulation (2020)

Introduction: Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures. Hypothesis: Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence. Methods: In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1 APOE ε4 alleles. Results: In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or APOE ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy. Conclusions: Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.
Livin, a regulator of apoptosis protein, is deregulated in melanoma and serves as an independent prognostic factor—a study of 114 melanoma patients
Authors: I. Lazar
Journal: Journal of Clinical Oncology (2007)

21006 Background: Inhibitor of Apoptosis Proteins (IAP) family members inhibit apoptosis mainly by direct binding and inhibition of caspases. We previously identified the IAP Livin and demonstrated that following strong apoptotic stimuli the protein was cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. We also demonstrated that Livin is overexpressed in melanoma (M) and plays a role in chemoresistance and survival. More recently we identified synonymous single nucleotide polymorphism (SNP) in Livin at position 528(C/T) that determines expression levels of Livin protein. We found that Livin is expressed in a monoalleic manner. Normal heterozygous samples express the 528T mRNA allele and the Livin protein is not expressed. The monoallelic regulation is lost in metastatic M and the Livin protein is expressed. Methods: This study included 114 M patients that were grouped into clinical categories according to prognosis. Correlation between Livin expression and clinical parameters was examined using ANOVA, chi-square test and Kaplan-Mayer curves. Results: We found that in primary cultures from 114 M patients high, low and absence of Livin protein expression were associated with the T/C, CC and TT genotypes, respectively, at the 528(C/T) polymorphic site. Correlation of Livin expression with overall survival was significant: high expression of the Livin protein was associated with bad prognosis; survival in patients with medium expression of Livin was significantly longer compared with those without livin expression For 23 patients samples were obtained both at diagnosis and upon disease progression. All 23 first tumor sample did not express the Livin protein. Remarkably, Livin was expressed in second tumor samples from 9 of the 23 patients.and was associated with poor prognosis. Conclusions: We found that Livin expression is an independent prognosis factor in malignant M. furthermore, we describe a direct correlation between the level of Livin protein expression and survival of M patients. We also provide evidence for a novel mechanism associating synonymous SNP with control over protein expression and its deregulation during tumor progression. No significant financial relationships to disclose.