tbuckley/cabot-search huggingface dataset:
Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial
Authors: Kerstin Schütte, Regina Schinner, Mathias P. Fabritius, Melina Möller, Christiane Kuhl, Roberto Iezzi, Osman Öcal, Maciej Pech, Bora Peynircioglu, Max Seidensticker, Rohini Sharma, Daniel Palmer, Jean-Pierre Bronowicki, Peter Reimer, Peter Malfertheiner, Jens Ricke
Journal: Liver Cancer (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, &lt;i&gt;n&lt;/i&gt; = 11; adrenal glands, &lt;i&gt;n&lt;/i&gt; = 5; peritoneum, &lt;i&gt;n&lt;/i&gt; = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (&lt;i&gt;p&lt;/i&gt; = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; &lt;i&gt;p&lt;/i&gt; = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, &lt;i&gt;p&lt;/i&gt; = 0.0060). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.
Hybrid Printing Using Cellulose Nanocrystals Reinforced GelMA/HAMA Hydrogels for Improved Structural Integration
Authors: Yuchao Fan, Zhilian Yue, Enrico Lucarelli, Gordon G. Wallace
Journal: Advanced Healthcare Materials (2020)

3D printing of soft-tissue like cytocompatible single material constructs with appropriate mechanical properties remains a challenge. Hybrid printing technology provides an attractive alternative as it combines a cell-free ink for providing mechanical support with a bioink for housing embedded cells. Several hybrid printed structures have been developed, utilizing thermoplastic polymers such as polycaprolactone as structural support. These thermoplastics demonstrated limited structural integration with the cell-laden components, and this may compromise the overall performance. In this work, a hybrid printing platform is presented using two distinct hydrogel inks that share the same photo-crosslinking chemistry to enable simple fabrication and seamless structural integration. A mechanically reinforced hydrogel ink is developed comprising cellulose nanocrystals and gelatin methacryloyl/hyaluronic acid methacrylate (GelMA/HAMA) as the structural component, and GelMA/HAMA as the cytogel containing a mouse chondrogenic cell line, ATDC5. Hybrid printed constructs with encapsulated cells are fabricated using the two optimized inks, and the structural integration of the constructs is evaluated by cyclic mechanical compression. Finally, the cell viability of encapsulated ATDC5 cells in the hybrid printed structures is evaluated.
Abstract 14404: The Fontan Udenafil Exercise Longitudinal Trial Subgroup Analysis
Authors: David J Goldberg, Russell Gongwer, Felicia Trachtenberg, Adam M Lubert, Jonathan Rhodes, Daniel J Penny, Christopher J Petit, Kurt R Schumacher, Salil Ginde, Richard V Williams, Ja Kyoung Yoon, Gi Beom Kim, Todd T Nowlen, Michael V DiMaria, Benjamin P Frischhertz, Jonathan B Wagner, Kimberly E McHugh, Brian W McCrindle, Mark Cartoski, Jon A Detterich, Angela T Yetman, Anitha S John, Marc E Richmond, Delphine Yung, Ronald M Payne, Andrew S Mackie, Christopher K Davis, Shabana Shahanavaz, Kevin D Hill, Marisa Almaguer, Michael G McBride, Bryan H Goldstein, Gail D Pearson, Stephen M Paridon
Journal: Circulation (2020)

Background: The Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT 02741115) demonstrated improvements in exercise capacity and ventricular performance following six months of treatment with udenafil (87.5 mg twice daily). In this analysis we evaluated whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. Methods: The effect of udenafil on exercise was evaluated within subgroups defined by gender, race, ventricular morphology, and baseline peak oxygen consumption (VO 2 ). Linear regression modeling evaluated for differential response to udenafil (interaction of subgroup with treatment arm). Individual subgroups were excluded if the number of participants was &lt;5% of total. As the FUEL Trial was not powered for subgroup analysis, all analyses were viewed as exploratory. Results: Subgroup analyses demonstrated qualitative improvements in peak VO 2 , work rate at the ventilatory anaerobic threshold (VAT), VO 2 at VAT, and ventilatory efficiency (VE/VCO 2 ) for those randomized to udenafil compared to placebo in all subgroups (Table). There was not a differential response to udenafil based on gender, race, ventricular morphology, or baseline peak VO 2 , although participants in the lowest tertile of baseline peak VO 2 and those with single left ventricles trended toward larger improvements. Conclusion: The relatively uniform improvement among subgroups in response to treatment with udenafil is consistent with the findings from the primary analysis of the FUEL trial. While the absence of a statistically significant differential effect between subgroups suggests that the effect of udenafil may not be gender, race, or morphology specific, and may not vary based on baseline exercise performance, the possibility of a larger improvements in those with poor baseline peak VO 2 and those with single left ventricle warrants further investigation.
Persistently activated, proliferative memory autoreactive B cells promote inflammation in rheumatoid arthritis
Authors: Hendy Kristyanto, Nienke J. Blomberg, Linda M. Slot, Ellen I. H. van der Voort, Priscilla F. Kerkman, Aleida Bakker, Leonie E. Burgers, Robin M. ten Brinck, Annette H. M. van der Helm-van Mil, Hergen Spits, Dominique L. Baeten, Tom W. J. Huizinga, René E. M. Toes, Hans U. Scherer
Journal: Science Translational Medicine (2020)

Autoreactive B cells mediate autoimmune pathology, but exactly how remains unknown. A hallmark of rheumatoid arthritis (RA), a common autoimmune disease, is the presence of disease-specific anticitrullinated protein antibodies (ACPAs). Here, we showed that ACPA-positive B cells in patients with RA strongly expressed T cell-stimulating ligands, produced abundant proinflammatory cytokines, and were proliferative while escaping inhibitory signals. This activated state was found at different degrees in different stages of disease: highest in patients with recent-onset RA, moderate in patients with established RA, and far less pronounced in ACPA-positive individuals "at risk" for developing disease. The activated autoreactive B cell response persisted in patients who achieved clinical remission with conventional treatment. ACPA-positive B cells in blood and synovial fluid secreted increased amounts of the chemoattractant interleukin-8, which attracted neutrophils, the most abundant immune cell in arthritic joints. Tetanus toxoid-specific B cells from the same patients exhibited properties of memory B cells without the activation and proliferation phenotype, but these cells transiently acquired a similar proliferative phenotype upon booster vaccination. Together, these data indicated that continuous antigenic triggering of autoreactive B cells occurs in human autoimmune disease and support the emerging concept of immunological activity that persists under treatment even in clinical remission, which may revise our current concept of treatment targets for future therapeutic interventions. In addition, our data pointed to a pathogenic role of ACPA-positive B cells in the inflammatory disease process underlying RA and favor approaches that aim at their antigen-specific inactivation or depletion.
Abstract 14484: The Association of Pre-operative Glycemic Control With Long-term Survival in Diabetic Patients After Coronary Artery Bypass Grafting
Authors: Muhammad Sheikh, Salil V Deo, Varun Sundaram, Brigid Wilson, Jayakumar Sahadevan, Joseph Rubelowsky, Srikrishna M Mohan, Richard A Josephson, Yakov Elgudin, Brian L cmolik
Journal: Circulation (2020)

Introduction: We analyzed the national Veteran Affairs (VA) data to evaluate the association of preoperative glycated Hemoglobin (HbA1c) and long-term outcome after isolated coronary artery bypass grafting (CABG). Methods: Between January 2007 - December 2014, Veterans with diabetes mellitus (DM) that underwent isolated CABG were divided on into three groups (I: HbA1c &lt; 8%, II: HbA1c 8 - 10% and III: HbA1c &gt; 10%). Demographic and clinical differences between groups were evaluated with the t-test or chi-square test. The relationship of preoperative HbA1c and long-term survival was evaluated with a multivariable proportional hazards model; restricted cubic splines were used to model non-linear effects. The cumulative incidence of secondary end-points (myocardial infarction, urgent revascularization) for each group was modeled as a competing-risk analysis. Results: Overall, 3,210 patients (mean age 64.6 years, male 98.8%; insulin dependent - 53%) with DM underwent isolated CABG. Group III patients were younger (61 vs 65 years in group I). Median HbA1c levels were similar between races (white - 7.3% and blacks - 7.35%). Insulin dependence was higher in group III (79.3%) vs groups I (43.5%) and II (69.9%). In groups I,II and III, 5 and 10 year survival was 76.2%, 74.4%, 75.4% and 38.9%, 36.9% and 30.2% respectively. HbA1c was observed to have a J-shaped association with mortality with values &lt; 6% and &gt; 9% at higher risk of death. Left ventricular systolic dysfunction [HR 1.5 (1.3 - 1.7)], prior myocardial infarction [HR 1.3 (1.2 - 1.5)] and insulin dependence [HR 1.4 (1.2 - 1.5)] were also associated with lower survival. Myocardial infarction was observed in 9.8% , 13.4% and 12.8% patients in groups I, II and III respectively. Conclusions: Pre-operative HbA1c impacts long-term survival among diabetic patients undergoing CABG. We observed a J-shaped relationship between HbA1c and survival with values &lt; 6% and &gt; 9% associated with increased mortality.
Double-surgical-mask-with-slit and COVID-19 prevention
Authors: Sora Yasri, Viroj Wiwanitkit
Journal: Endoscopy (2020)

See also: "Double-surgical-mask-with-slit" method: reducing exposure to aerosol generation at upper gastrointestinal endoscopy during the COVID-19 pandemicEndoscopy 2020; 52(10): 928-929DOI: 10.1055/a-1198-5471 See also: Reply to Letter to the Editor, Reply to Yasri & WiwanitkitEndoscopy eFirstDOI: 10.1055/a-1303-9528
Abstract 13680: Icosapent Ethyl Therapy for Patients With an Established Cardiovascular Disease Provides Significantly More Value for Money Than When Prescribed as Primary Prevention
Authors: Ronen Arbel, Enis Aboalhasan, Ariel Hammerman, Joseph Azuri
Journal: Circulation (2020)

Introduction: Icosapent ethyl is currently the only drug approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia, who are already on statin therapy. The approved use is both for secondary prevention in patients with established cardiovascular disease (CVD) or primary prevention for patients with diabetes and multiple risk factors. Despite its’ proven clinical benefits, the addition of icosapent ethyl to patient’s current treatment regimens may impose a significant cost burden on healthcare systems. Hypothesis: Prioritizing icosapent ethyl therapy for patients with an established CVD may provide significantly more value for money than when prescribed as primary prevention. Methods: We performed an analysis of the cost required for icosapent ethyl per achieved outcome when prescribed either for primary or for secondary prevention of MACE. The cost needed to treat (CNT) to prevent one MACE in the REDUCE-IT trial was estimated by multiplying the annualized number needed to treat to prevent one event, by the annual cost of therapy. The market price of icosapent ethyl in the US was estimated as 75% of the US national average drug acquisition cost listing. Results: In the REDUCE-IT population, the figured CNT of Icosapent ethyl provided as primary prevention was $874,500 (95% CI: $349,800-∞) vs. $206,965 (95% CI: $160,325-$294,415) for secondary prevention; P&lt;0.001. Conclusions: The CNT for patients receiving the drug for primary prevention of MACE was four-fold higher than when provided as secondary prevention. Our findings suggest that icosapent ethyl therapy for patients with an established CVD provides significantly more value for money.
Abstract 14950: <i>SLCO1B1</i> Genotype is Associated With Atorvastatin Discontinuation
Authors: Deepak Voora, Jordan Baye, Adam D Mcdermaid, Smitha N Gowda, Larson A Eric, Wilke A Russell
Journal: Circulation (2020)

Introduction: Atorvastatin is commonly prescribed to prevent cardiovascular disease; however, long-term adherence can be eroded by statin associated musculoskeletal symptoms (SAMS). Genetic variants in SLCO1B1 are associated with SAMS in patients using simvastatin; the association of these variants with adherence or SAMS has been less well characterized for atorvastatin. Methods: We tested the association between a loss of function genetic variant in SLCO1B1 and atorvastatin discontinuation in a large multi-specialty group practice. Using the electronic medical record (EMR) at Sanford Health, we defined a retrospective cohort of 8453 patients who were tested for SLCO1B1*5 (rs4149056, Val174Ala) through routine clinical care. Patients were included if they had received an atorvastatin prescription prior to genetic testing and had valid SLCO1B1 results. Patients were classified as discontinued (or not) based on their active medication list at the time of genetic testing. Clinical characteristics including demographics, diagnosis codes, smoking status, concomitant medications, and laboratory values for renal function and all creatine kinase (CK) values prior to testing, were extracted from the EMR. A Kruskal-Wallis test was used to compare longitudinal CK values vs. discontinuation. Logistic regression was used to test the relationship between SLCO1B1*5 and atorvastatin discontinuation for any reason. Results: There were 1752 patients available for analysis (mean age 64 years, 44% female, 2% non-Caucasian, 89% primary prevention indication). 1025 (58%) discontinued atorvastatin prior to SLCO1B1 testing. The number of SLCO1B1*5 alleles was associated with atorvastatin discontinuation (odds ratio per allele = 1.22, 95% confidence interval = 1.004 - 1.47, p = 0.04). Among the 495 patients with available CK levels, atorvastatin discontinuation was associated with higher mean CK levels than those who continued (Kruskal-Wallis test, p = 0.02). Conclusions: Atorvastatin discontinuation is common in real world patients at risk for cardiovascular disease. Carriers of SLCO1B1*5 are at increased risk for premature atorvastatin discontinuation - an effect which may reflect an excess risk of statin myopathy.
Transparency, trust, and community welfare: towards a precision public health ethics framework for the genomics era
Authors: Eric T. Juengst, Annelies Van Rie
Journal: Genome Medicine (2020)

Abstract Infectious disease control is experiencing a paradigm shift, as pathogen sequencing technologies and digital applications are increasingly implemented for control of diseases such as tuberculosis, Ebola, and COVID-19. A new ethical framework should be a critical part of this emerging paradigm to ensure that the benefit of precision public health interventions based on advances in genomics research is not outweighed by the risks they pose to individuals, families, and vulnerable segments of the population. We suggest that the ethical framework guiding practice in this domain combines standard precepts from public health ethics with emerging ethics principles from precision medicine.
Combined Assessment of Myocardial Perfusion and Late Gadolinium Enhancement in Patients After Percutaneous Coronary Intervention or Bypass Grafts
Authors: Peter Bernhardt, Jochen Spiess, Benny Levenson, Günter Pilz, Berthold Höfling, Vinzenz Hombach, Oliver Strohm
Journal: JACC. Cardiovascular imaging (2009)
Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets
Authors: Renata Ferrarotto, Yoshitsugu Mitani, Daniel J. McGrail, Kaiyi Li, Tatiana V. Karpinets, Diana Bell, Steven J. Frank, Xingzhi Song, Michael E. Kupferman, Bin Liu, J. Jack Lee, Bonnie S. Glisson, Jianhua Zhang, Jon C. Aster, Shiaw-Yih Lin, P. Andrew Futreal, John V. Heymach, Adel K. El-Naggar
Journal: Clinical Cancer Research (2020)

Salivary gland adenoid cystic carcinoma (ACC) has heterogeneous clinical behavior. Currently, all patients are treated uniformly, and no standard-of-care systemic therapy exists for metastatic ACC. We conducted an integrated proteogenomic analyses of ACC tumors to identify dysregulated pathways and propose a classification with therapeutic implications.RNA/DNA sequencing of 54 flash-frozen salivary ACCs and reverse phase protein array (RPPA) in 38 specimens were performed, with validation by Western blotting and/or IHC. Three independent ACC cohorts were used for validation.Both unbiased RNA sequencing (RNA-seq) and RPPA analysis revealed two molecular subtypes: ACC-I (37%) and ACC-II (63%). ACC-I had strong upregulation of MYC, MYC target genes, and mRNA splicing, enrichment of NOTCH-activating mutations, and dramatically worse prognosis. ACC-II exhibited upregulation of TP63 and receptor tyrosine kinases (AXL, MET, and EGFR) and less aggressive clinical course. TP63 and MYC were sufficient to assign tumors to ACC subtypes, which was validated in one independent cohort by IHC and two additional independent cohorts by RNA-seq. Furthermore, IHC staining for MYC and P63 protein levels can be used to identify ACC subtypes, enabling rapid clinical deployment to guide therapeutic decisions. Our data suggest a model in which ACC-I is driven by MYC signaling through either NOTCH mutations or direct amplification, which in turn suppress P63 signaling observed in ACC-II, producing unique therapeutic vulnerabilities for each subtype.Cooccurrence of multiple actionable protein/pathways alterations in each subtype indicates unique therapeutic vulnerabilities and opportunities for optimal combination therapy for this understudied and heterogeneous disease.
Abstract 277: Discrepancies Between Non-invasive Blood Pressure Monitor Data and Ems Provider Documentation in Major Traumatic Brain Injury: Are We Missing Hypotension?
Authors: Daniel W Spaite, Bruce J Barnhart, Eric Helfenbein, Dawn B Jorgenson, Saeed Babaeizadeh, Joshua B Gaither, Amber D Rice, Samuel M Keim, Gail Bradley, Chengcheng Hu
Journal: Circulation (2020)

Background: Recent studies have shown that prehospital systolic blood pressure (SBP) is strongly associated with mortality across a remarkably wide range (far above 90 mmHg) in traumatic brain injury (TBI). Furthermore, in TBI research, trial enrollment and risk-adjustment are highly dependent upon accurate documentation of BP. Our preliminary work identified potential discrepancies between EMS-documented vs. actual measured BP. Objective: In major TBI, evaluate concordance between SBP documented in EMS patient care records (PCR) and actual, monitor-recorded SBP. Methods: A subset of major TBI cases (mod/severe/critical) in the EPIC TBI Study (NIH 1R01NS071049) were analyzed (3/13-7/18). Cases from 6 EMS agencies reporting continuous monitor data (Philips MRx™) were included. All monitor data available for this analysis were displayed and accessible to the providers during EMS care. We compared the lowest PCR-documented SBP to the monitor-recorded value in each patient. Results: Included: 210 cases (median age: 52, 67% male). In 152 cases (72%), the lowest PCR-documented SBP was exactly concordant with the monitor. When concordance was defined by a difference of ≤5 mmHg, 171 (81%) were concordant. Among the 27 cases with monitor-identified hypotension (&lt;90 mmHg), only 18 (67%) were documented by EMS. EMS documentation also failed to record 20% (3/15) of “near-hypotensive” cases (90-99 mmHg). Conclusions: Significant disparities existed between monitor-recorded and PCR-documented SBP. PCRs failed to reflect 33% of monitor-documented hypotensive cases. It appears that ongoing care responsibilities and scene distractions may cause providers to miss important BP readings. These findings identify a potential hidden contributor to poor outcomes if hypotension goes unrecognized and untreated, rather than simply not being documented. Furthermore, case ascertainment, trial enrollment, confounding, and risk-adjustment in TBI studies may be substantially impacted when these processes are based on EMS documentation. When possible, QI and research projects should utilize monitor data to identify hypotensive patients. Development of real-time audiovisual monitor feedback technology might improve provider recognition of hypotension.
Antibiotic Susceptibility of <i>Escherichia coli</i> Among Infants Admitted to Neonatal Intensive Care Units Across the US From 2009 to 2017
Authors: Dustin D. Flannery, Ibukunoluwa C. Akinboyo, Sagori Mukhopadhyay, Alison C. Tribble, Lihai Song, Feiyan Chen, Yun Li, Jeffrey S. Gerber, Karen M. Puopolo
Journal: JAMA Pediatrics (2020)

Escherichia coli is a leading cause of serious infection among term and preterm newborn infants. Surveillance of antibiotic susceptibility patterns of E coli among infants admitted to neonatal intensive care units should inform empirical antibiotic administration.
Top authors in dermatology by h-index: A bibliometric analysis of 1980-2020
Authors: Mindy D. Szeto, Colby L. Presley, Mayra B.C. Maymone, Melissa R. Laughter, Steven M. Lada, Taylor M. Runion, Cara Barber, Allene Fonseca, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2020)