tbuckley/cabot-search huggingface dataset:
Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study
Authors: Ping Zhang, Karen M. Atkinson, George A. Bray, Haiying Chen, Jeanne M. Clark, Mace Coday, Gareth R. Dutton, Caitlin Egan, Mark A. Espeland, Mary Evans, John P. Foreyt, Frank L. Greenway, Edward W. Gregg, Helen P. Hazuda, James O. Hill, Edward S. Horton, Van S. Hubbard, Peter J. Huckfeldt, Sharon D. Jackson, John M. Jakicic, Robert W. Jeffery, Karen C. Johnson, Steven E. Kahn, Tina Killean, William C. Knowler, Mary Korytkowski, Cora E. Lewis, Nisa M. Maruthur, Sara Michaels, Maria G. Montez, David M. Nathan, Jennifer Patricio, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, Bruce Redmon, Julia T. Rushing, Helmut Steinburg, Thomas A. Wadden, Rena R. Wing, Holly Wyatt, Susan Z. Yanovski
Journal: Diabetes Care (2020)

OBJECTIVE To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.
Case of Merkel cell carcinoma in a patient with pre-existing ILD
Authors: Rohan Maniar, Michaela Anderson, Bret Taback, Shaheer Khan, Diana McDonnell, Anjali Saqi, George W Niedt, Richard Carvajal
Journal: Journal for ImmunoTherapy of Cancer (2020)

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin with high rates of local recurrence and distant metastases despite treatment with traditional cytotoxic chemotherapies. The recent advances in immunotherapy, including the use of immune checkpoint blockade (ICB) has revolutionized treatment for this disease and resulted in durable responses for some patients. However, many patients, due to underlying conditions, have been insufficiently evaluated for potential use of immunotherapy. Here we present a case of ICB treatment with Programmed cell death protein 1 (PD-1) inhibition in a patient with underlying interstitial lung disease (ILD) and a new diagnosis of MCC. Through a multidisciplinary approach, we were able to maintain close monitoring with serial clinical and radiographical follow-up. The patient achieved a complete response though unrelated medical issues resulting in a treatment hold. At the last follow-up, the patient continued to experience a durable response without evidence of recurrence. This case describes the use of pembrolizumab, a PD-1 inhibitor, for the treatment of MCC in a patient with underlying ILD. The use of active surveillance with a multidisciplinary approach resulted in successful treatment of MCC without exacerbation of the underlying ILD.
Abstract 15749: Sex-differences in Coronary Heart Disease Between Individuals With Familial Hypercholesterolemia and Controls in Norway During 1992-2017
Authors: Karianne Svendsen, Jannicke Igland, Henriette W Krogh, Grethe S Tell, Liv J Mundal, Kirsten B Holven, Martin P Bogsrud, Trond P Leren, Kjetil Retterstol
Journal: Circulation (2020)

Introduction: During the last 30 years, treatment of familial hypercholesterolemia (FH) has been revolutionized, but it is not known if both sexes equally benefit in these advances, and whether this could have affected the sex difference in risk of coronary heart disease (CHD). We aimed to study sex difference in the risk of CHD between men and women with FH compared to non-FH men and women. Methods: We obtained data on CHD hospitalization and death from Norwegian health registries in 4,525 individuals diagnosed with FH between 1992 and 2014 and an age and sex matched control population of 88,892. The sex distribution was about 50/50 between women and men, and the mean age at start of follow-up was 36 years. Results: The cumulative incidence of CHD (FH vs. non-FH controls) in women and men are shown in Figure 1 with a clear increased risk in FH compared to controls. The cumulative incidence starts to increase at a younger age in men compared with women, both in FH and non-FH controls. This corresponds to an age adjusted 2.6-fold higher risk of CHD in men compared with women in both the FH and control population. In the FH population, men aged 20-39 years had a hazard ratio (HR) of 5.3 (95% CI: 2.6-10.9) compared with women, whereas the corresponding HR between women and men in non-FH controls was 3.7 (95% CI: 2.6-5.3). There was no significant interaction between sex and FH status, indicating that the excess risk in men was similar in FH and non-FH controls. Stratified by sex and adjusted for age, we found that both men and women with FH had a 2-fold higher risk of CHD than controls. The highest excess risk was observed in ages 20-30 years with a of HR= 4.5 (95% CI: 2.2-9.2) and a HR of= 5.5 (95%CI: 4.60-9.34) in women and men, respectively. Conclusions: The risk of CHD among individuals with FH was higher in men than in women in all age groups presented, with no differences between the FH sample and the non-FH controls. However, the relative risk in FH compared with controls was similar for both sexes.
Abstract 14529: Management of Acute Myocardial Infarction in a Patient With a Left Ventricular Assist Device
Authors: Kevin A Friede, Vanessa Blumer, James Tcheng, William Jones, Manesh R Patel, Richa Agarwal
Journal: Circulation (2020)

Introduction: We present a case of an LVAD patient presenting with nonspecific symptoms found to have type I MI due to critical LAD stenosis. Case Presentation: A 65-year-old male patient with a HeartMate II LVAD as destination therapy for ischemic cardiomyopathy presented with chest pain and generalized malaise. Examination demonstrated euvolemia and no stigmata of infection or thromboembolism. Labs were notable for an INR of 1.4 and high-sensitivity troponin values of 792 and 886 ng/L (ULN, 53 ng/L). ECG showed old anterior and inferior infarct; echocardiography revealed an LVEF of 20% with mild RV dysfunction and an immobile aortic valve. Non-atherosclerosis-related causes of MI were initially explored: CT of the chest and abdomen did not show infection or PE, and LVAD interrogation did not show any abnormal power trends or flows. Coronary angiography showed a 99% ostial LAD lesion, clearly progressed compared to 3 years earlier (Figures 1A and 1B). PCI with a drug-eluting stent restored normal flow (Figure 1C) with prompt resolution of symptoms. The patient is doing well over 1 year after PCI. Discussion: Acute MI is uncommon in LVAD patients and may present differently from a traditional CAD population due to the impact of the device on myocardial wall stress and oxygen demand through direct and continuous LV unloading. Case series of PCI in durable LVAD patients generally identify right heart failure, VT, or embolized thrombus from an immobile aortic valve, rather than a type I MI, as the primary indication. There is a paucity of data regarding the best approach for anticoagulation and antiplatelet management in LVAD patients after PCI. Conclusion: Type I MI should be considered in the right clinical context in LVAD patients presenting with elevated cardiac biomarkers, recognizing the potential for reduced specificity of clinical and ECG data. Future study of the long-term outcomes and appropriate secondary management of LVAD patients undergoing PCI is needed.
Abstract 16769: Intravenous Injection of Neonatal Cardiac Mesenchymal Stem Cells is a Viable Alternative Route to Treat Acute Myocardial Infarction
Authors: Progyaparamita Saha, Rachana Mishra, Sudhish Sharma, Aakash Shah, Lauren Davidson, Muthukumar Gunasekaran, Xuebin Fu, Mir Arfat, Mohamed Abdullah, Deqiang Li, Sunjay Kaushal
Journal: Circulation (2020)

Introduction: Cardiovascular disease is major cause of morbidity and mortality around the world and major health care burden indeed. Ischemic heart disease (IHD) and myocardial ischemia (MI) are most devastating cardiovascular disease. Multiple stem cell/ cardiac progenitor cell therapy has been reported previously to treat cardiovascular disease safely. However randomized clinical trials with adult cardiac progenitor cells or cardiosphere-derived cells unable to show long-term efficacy. We have our unique source of human neonatal cardiac tissue derived neonatal cardiac mesenchymal stem cells (nMSCs). Systemic administration is preferred route of stem cell delivery in order to consecutive dosage for most of the clinical trials. We hypothesized that nMSCs have unique proteome profile, which supports their survival, migration and homing. They home to the injured myocardium when administered intravenously (IV) to a wild type male rat subjected to MI. Methods: This model was created in 6-week-old Brown-Norway Rats. Rats were subjected to an anterior myocardial Infraction (MI) by permanent LAD ligation. The rats were treated with nMSCs (1^10 6 cells/Kg, 5^10 6 cells/Kg and 10^10 6 cells/Kg) along with placebo and sham, which are delivered intravenously by tail vein injection. Rats are once again treated with nMSCs/placebo 4 days after MI. Baseline echocardiography is performed 24 hours after MI. Results: LVEF was significantly higher in the nMSC-treated group than in the placebo group. Other parameters, including fractional shortening (FS) and decreased end-systolic volume (ESV), were also significantly improved when compared with the placebo group, and other LV functional parameter, including cardiac output/body weight and posterior wall thickness tended towards improvement of remodeled heart. Conclusions: Twice intravenous administration of nMSCs for MI attenuate the progressive deterioration of left ventricle and adverse remodeling of rat heart.
Abstract PO-068: Intratumoral heterogeneity of prognostic multigene signatures for breast cancer
Authors: Amber N. Hurson, Alina Hamilton, Linnea T. Olsson, Erin L. Kirk, Benjamin C. Calhoun, Joseph Geradts, Mark E. Sherman, Melissa A. Troester
Journal: Cancer Research (2020)

Abstract Background Multigene assays for breast cancer are becoming more commonly used for research, diagnostic, and treatment-selection purposes. These assays are commonly based on a single tumor sample, so this study assesses whether clinically-relevant multigene scores are subject to misclassification due to technical variation or intratumoral heterogeneity. Methods Using FFPE blocks, tumors from 37 patients were sampled at different pathologist-selected spatial locations, targeting regions with distinct histological appearance. A second pathologist assessed mitotic activity and presence of immune infiltration for each specimen. Gene expression was quantified using the PAM50 assay. Samples were classified with respect to intrinsic subtype (Luminal A, Luminal B, HER2-enriched, or Basal-like) and risk of recurrence with proliferation score (ROR-P, high vs. med/low). Euclidean distances between samples were calculated across the 50 genes, and the distribution of Euclidean distances were compared for samples that were concordant vs. discordant for each multigene classifier for PAM50 or ROR-P. Results Of the 37 tumors, 11 had samples with discordant PAM50 subtype and 7 had samples with discordant ROR-P group (75% and 83% agreement, respectively). The Euclidean distance between paired samples with discordant PAM50 intrinsic subtype or ROR-P score was significantly greater than that among concordant tumors. Samples discordant for ROR-P had more heterogeneity in histological characteristics, while discordance of PAM50 subtype call was generally not predicted by heterogeneity of these histological characteristics. Conclusion The concordance of PAM50 subtype calls and ROR-P, despite oversampling of heterogenous-appearing tumor regions, demonstrates reproducibility of the PAM50 classifier for breast cancer tumor intrinsic subtyping. However, assay sampling strategies for histologically heterogeneous tumors merit further consideration. Citation Format: Amber N. Hurson, Alina Hamilton, Linnea T. Olsson, Erin L. Kirk, Benjamin C. Calhoun, Joseph Geradts, Mark E. Sherman, Melissa A. Troester. Intratumoral heterogeneity of prognostic multigene signatures for breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-068.
ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma
Authors: Maria Arechederra, Sehrish K. Bazai, Ahmed Abdouni, Celia Sequera, Timothy J. Mead, Sylvie Richelme, Fabrice Daian, Stéphane Audebert, Rosanna Dono, Anthony Lozano, Damien Gregoire, Urszula Hibner, Daniela S. Allende, Suneel S. Apte, Flavio Maina
Journal: Journal of Hepatology (2020)
AB0139 Impact of obesity on degenerative radiographic findings
Authors: A Atalay, S Arslan, R Çeliker
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Obesity is a growing problem in all countries which is considered to be one of the most important concerns for public health. For clarification of the topic, further research about morbidity of the problem should be considered. <h3>Objectives</h3> The purpose of this study was to assess degenerative radiographic findings of the spine, pelvis and knees related with obesity. <h3>Methods</h3> 71 female patients from our outpatient clinics were enrolled in the study. Cut-off points for obesity were determined according to guidelines of World Health Organisation (WHO). Cut-off values are as follows: 18.5–24.99: normal, 25.0–29.99 grade1 overweight, 30.0–39.99 grade 2 overweight, &gt; = 40.0 grade 3 overweight. Beside demographic data, radiologic assessment by plain radiographs of the spine, pelvis and knees were obtained. Antropometric measurements including height, body weight, abdominal circumference, waist circumference, triceps skinfold thickness were performed by the same physician. Body mass index (BMI) was calculated as kg/m<sup>2</sup>. Radiographs were evaluated by a physician blind to the clinical status of that particular patient. For radiologic evaluations Kellgren-Lawrence score was utilised. p &lt; 0.05 was considered to be statistically significant. <h3>Results</h3> The mean age of the subjects was 52.70 ± 11.25 years (range: 25–78 years) and mean BMI was 31.17 ± 5.70 (range: 21.91–47.27). Degenerative changes in lumbar spine and knees are shown in Table 1. BMI was positively correlated with degenerative changes in the knee even when controlled for age (p = 0.000). Radiographs of the knee was also found to be correlated with body weight abdominal circumference, waist circumference, triceps skinfold thickness. Radiologic score of the knees were found to be correlated with scores of the pelvis and lumbar spine. But radiologic scores of pelvis and lumbar spine were not correlated with antropometric measures. <h3>Conclusion</h3> Radiographic findings in the knee was found to be correlated with BMI and other anthropometric measures when controlled for age but there was no correlation between obesity and radiographs of the pelvis and lumbar spine. <h3>References</h3> Felson DT, Zhang Y, Anthony JM, <i>et al</i>. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. Ann Intern Med. 1992;116:535–9 Sharma L, Lou C, Cahue S, <i>et al</i>. The mechanism of the effect of obesity in knee osteoarthritis. Arthritis Rheum. 2000;43:568–75 Stürmer T, Günther KP, Brenner H. Obesity, overweight and patterns of osteoarthritis: The Ulm Osteoarthritis Study. J Clin Epidemiol. 2000;53:307–13
Abstract 15260: Self DNA From Damaged Smooth Muscle Cells Drives Inflammatory Response in Macrophages by Activating Cytosolic DNA Sensor STING --- An Implication in Vascular Injury and Inflammation
Authors: Yidan Wang, Wei Luo, Lin Zhang, Pingping Ren, Jiao Guo, Chen Zhang, Chris Guardado, Joseph S Coselli, Scott A LeMaire, Ying H Shen
Journal: Circulation (2018)

Introduction: During tissue injury, damaged cells activate inflammatory cells, which in turn produce destructive proteins and promote further injury, leading to disease progression. Understanding t...
Abstract 13356: Who Doesn't Respond to Motivational Interviewing for Heart Failure Self-care?
Authors: Michael A Stawnychy, Valentina Zeffiro, Paolo Iovino, Ercole Vellone, Barbara J Riegel
Journal: Circulation (2020)

Background: Motivational interviewing (MI) improves HF self-care yet fails to work for some patients. Lack of intervention response leaves clinicians and patients with fewer treatment options. Aim: Identify the characteristics of non-responders to MI in adults with HF. Methods: Secondary analysis of intervention group ( n =230) from MOTIVATE-HF trial. Study conducted in Italy to evaluate effectiveness of MI in improving HF self-care. Self-care maintenance measured with the validated Self-care of Heart Failure Index (SCHFI) v6.2 at baseline and 3 months from enrollment. Standardized scores range 0-100; changes &gt; 7 pts from baseline are clinically significant. Participants dichotomized: MI non-responder (change in SCHFI &lt; 7 pts) vs MI responder (change in SCHFI ≥ 7 pts). Logistic regression, adjusted for group differences (employment, income, living alone, HF etiology, baseline self-care, cognitive impairment, mutuality, medications, sleep quality, and HF health status), was used to estimate odds ratio with 95% confidence interval (OR [95% CI]) to identify determinants of non-response. Results: Half of the intervention group were non-responders to MI ( n =115) at 3 months. Non-responders were 72±13 years old and 53% male. Twice the number of non-responders were employed ( n =36 vs n =18, p &lt;.005) and many reported ‘more than enough’ income (23% vs 13%, p &lt;.046). They had more non-ischemic HF (79% vs 54%, p &lt;.001), higher baseline self-care maintenance (48.8±19.2 vs 43.5±12.0, p &lt;.009), and took fewer medications (6.1±3.0 vs 7.6±2.5, p &lt;.009). Patients who responded to MI had worse HF quality of life ( p &lt;.018), more sleep disturbances ( p &lt;.042), and worse sleep quality ( p &lt;.002). Significant risk factors for non-response were non-ischemic HF (2.606 [1.340-5.071], p &lt;.005), fewer daily medications (0.829 [0.738-0.931], p &lt;.002), and better baseline self-care maintenance (1.025 [1.001-1.050], p &lt;.039). These variables explained 31% of HF self-care maintenance at 3 months (Nagelkerke R 2 =.309). Conclusion: MI may be less beneficial for patients with non-ischemic HF, lower medication burden, and relatively better self-care. Identifying characteristics of non-responders to MI in HF contributes to clinical decision making and personalized interventions.
Recurrent colonic polyps
Authors: Joseph Aslan, Thomas E Conley, Fiona Campbell, Philip J Smith, Frances McNicol, Timothy Andrews, Sreedhar Subramanian
Journal: Gut (2020)

A 56-year-old man presented with a change in bowel habit to seven loose non-bloody stools a day. He had previously had a sigmoid resection for an endoscopic diagnosis of colonic malignancy in 2015. Histology of the resection specimen, however, had only shown inflammatory polyps, attributed to the accompanying diverticular disease.

His current colonoscopy showed two malignant looking lesions in the descending colon (figure 1) and the hepatic flexure (figure 2) with multiple additional sub-5 mm polyps in the ascending colon (figure 3). The intervening colonic mucosa was inflamed with appearances suggesting ulcerative colitis. A CT scan showed a 12 cm segment of thickening at the hepatic flexure. Mucosal biopsies showed chronic active inflammation in the intervening mucosa in keeping with ulcerative colitis but there was …
Abstract 15489: Altered Biomechanical Properties of PKP2-deficient Hl-1 Cardiac Cells
Authors: Luca Puzzi, Valentina Martinelli, Marek Weiss, Priyatansh Gurha, Ali J Marian, Orfeo Sbaizero
Journal: Circulation (2015)

Arrhythmogenic cardiomyopathy (AC) is a genetic disease caused by mutations in genes encoding the intercalated disk (ID) proteins. ID is a multiprotein complex providing cell-cell junction and connecting the nucleus to the extracellular matrix, and playing a pivotal role for maintaining the structural integrity of the heart tissue. Mutations in PKP2 encoding plakophilin 2 (PKP2) are the most common causes of AC. The objective of this study was to investigate the biomechanical properties of the PKP2-knock down HL-1 mouse cardiac myocytes (PKP2-KD). PKP2 protein levels were reduced by 66 to 75% upon shRNA-targeting of the Pkp2 mRNA. Nuclear stiffness (Young’s modulus) and the force required to deform the nucleus were assessed by atomic force microscopy (AFM). Nuclear stiffness was decreased significantly (5 times) in PKP2-KD HL-1 myocytes as compared to wild-type (WT) myocytes, indicating an increased elasticity and/or susceptibility of the nucleus to be deformed (2 times). Interestingly, cell adhesion was also reduced (10 times) in the PKP2-KD myocytes, indicating a pivotal role of ID proteins in maintaining cell adhesion and mechanical integrity in cardiomyocytes. In the stress-relaxation test, while the decay time value was comparable between WT and PKP2-KD cells, relaxation force and cell deformation values were decreased 3 and 8 times, respectively, in PKP2-KD HL-1 myocytes, confirming the finding in the Young’s modulus. Moreover, the relaxation test revealed a reduced viscosity, highlighting a compromised cytoskeletal stability induced by the PKP2 deficiency. RNA-Sequencing and Ingenuity Canonical Pathway analysis identified integrin, tight junction, and the canonical Wnt signaling, among the most disturbed pathways in the PKP2-KD HL-1 myocytes. The findings indicate that the deficiency of a component of the ID protein markedly affects the whole-cellular biomechanics, which is expected to affect tissue stability, leading to activation of the mechano-transduction pathways.