tbuckley/cabot-search huggingface dataset:
Abstract 15268: Development of a Reliable Means of Assessment of Liver Function After the Fontan Operation: Dual Cholate Clearance Assay
Authors: Yuli Y Kim, Greg Everson, Steve Helmke, Jessica Carducci, Andrew C Glatz, Sara L Partington, Emily Ruckdeschel, Jack Rychik, Maarouf Hoteit
Journal: Circulation (2020)

Introduction: Currently there is no biomarker or test to accurately measure liver function in Fontan-associated liver disease. The dual cholate test (HepQuant SHUNT) is a noninvasive, flow-dependent assay measuring hepatic clearance of a bile acid, cholate, and may serve as a useful measure of liver function in the Fontan. We aim to measure cholate clearance in a cohort of Fontan patients and compare to normal controls. Methods: Single center, prospective pilot study of Fontan patients ≥ 18 years. Hepatic clearance of orally administered d4-cholate and intravenously administered 13C-cholate were measured in peripheral venous samples after 5, 20, 45, 60, and 90 minutes. Portal hepatic filtration rate (HFR), systemic HFR, shunt fraction (systemic HFR/portal HFR), and disease severity index (DSI) were calculated. Decline in HFRs and increase in shunt fraction or DSI is indicative of impaired liver function. Two-sided t-tests were used to compare values between Fontans and controls. Results: Twelve Fontan patients were enrolled (33% female, median age 29.9 [range 23.6 - 41.0] years). Median total bilirubin was 0.8 (range 0.3-2.1) mg/dL, AST 30.5 (range 16-55) U/L, ALT 32 (range 11-53) U/L, alkaline phosphatase 87 (range 42-191) U/L and platelets 177 (range 130-428) 10 3 /μL. Mean cardiac index was 3.0 ± 0.5 L/min/m 2 . Cholate clearance was lower in Fontans compared to controls (Figure). Mean portal HFR (mL/min/kg) in Fontans was lower than controls (15.1 ± 10.9 vs 29.1 ± 9.0; p&lt;0.001) as well as systemic HFR (3.7 ± 1.3 vs 6.5 ± 1.5; p&lt;0.001) whereas shunt fraction (%) was not (29.2 ± 11.4 vs 24.1 ± 7.5; p=NS). DSI was higher in Fontans compared to controls (19.4 ± 6.1 vs 9.2 ± 3.4; p&lt;0.001). Conclusions: Fontan patients demonstrate reduced hepatic function compared to normal controls but there is considerable variability. Future studies using the dual cholate test will examine the relationship between liver and cardiac function, as well as risk of adverse clinical outcome, in the Fontan.
Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update
Authors: Masatoshi Kudo
Journal: Liver Cancer (2020)

Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.
HP0029 An audit of the records of a rheumatology telephone helpline
Authors: JM Mooney, A Brooksby
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatology nurse practitioners provide advice, support and information via a telephone helpline. Patients, carers and health professionals access this service. The U. K. C. C. (1998) states that record keeping is an integral component of nursing and should reflect an accurate account of care given. <h3>Objective</h3> An audit was undertaken to discover whether the written documentation of the telephone helpline was recorded satisfactorily. <h3>Method</h3> A retrospective audit of all calls logged over a three- month period was analysed. The forms were examined to determine if they met the following standards. The date, time and who called should be noted. The nature of the call and the advice or information given should be recorded. All entries should be legible and signed. <h3>Results</h3> 393 calls were received over a three-month period. Of these 122 (31%) were medication queries, 67 (17%) treatment inquires, 8(2%) requests for a sooner appointment, 74(19%) questions regarding appointment, 28 (7%) required advice about disease flare up, 35 (9%) test results, 24 (6%) received reassurance and support. There were 4 (1%) enquires about Disability Living Allowance and 31 (8%) concerning other queries. On all forms the date was recorded in 97%, time 60%, details of who called 99% and type of call 26%. The entries were signed legibly in 95% and written comments were legible in 78% of cases. In 5% of forms the written information was unclear and poorly documented. <h3>Discussion</h3> This audit highlighted several problems with the existing documentation. Space was insufficient to record all details, urgent calls needed to be identified and an additional section was necessary for calls that could not be answered immediately. As a result a new documentation sheet has been designed. The importance of accurate, written documentation is vital in today’s health care and good quality record keeping improves communication and demonstrates evidence of good practice <h3>Reference</h3> United Kingdom Central Council for Nursing, Midwifery and Health Visiting. Guidelines for Records and Record Keeping, London, 1998
Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma
Authors: April K.S. Salama, Manisha Palta, Christel N. Rushing, M. Angelica Selim, Kristen N. Linney, Brian G. Czito, David S. Yoo, Brent A. Hanks, Georgia M. Beasley, Paul J. Mosca, Chelsae Dumbauld, Katelyn N. Steadman, John S. Yi, Kent J. Weinhold, Douglas S. Tyler, Walter T. Lee, David M. Brizel
Journal: Clinical Cancer Research (2020)

In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.
Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study
Authors: Francesca Watson, Maddalena Ardissino, Ravi J Amin, Chanpreet Arhi, Peter Collins, Osama Moussa, Sanjay Purkayastha
Journal: Circulation (2020)

Introduction: Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM. Hypothesis: Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM. Methods: A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually. Results: Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls. Conclusions: In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.
Abstract 13144: Epsilon Waves on Electrocardiograms in Pulmonary Hypertensive Patients With and Without Right Ventricular Hypertrophy or Fibrosis: Comparison With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Nobusada FUNABASHI, Yoshio Kobayashi
Journal: Circulation (2020)

Introduction: Epsilon waves on V1-3 leads are one of the specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) that suggest the presence of RV conduction delay. Hypothesis: In patients with pulmonary hypertension (PH) due to RV pressure load, RV hypertrophy and fibrosis are frequently observed that may lead to RV conduction delay and epsilon waves. Methods: We retrospectively analyzed 43 PH patients (33 females, 55 ± 15 years, 31 chronic thromboembolic PH, seven idiopathic pulmonary arterial hypertension), with proven PH by right heart catheterization. On CT, RV fibrosis was defined as a contrast defect in the early phase and a conversely abnormal enhancement in the late phase. We also retrospectively analyzed 17 patients (11 males, 57 ± 17 years) with suspected ARVC who underwent cardiac CT. Of these, nine met 2010 ARVC task force criteria on cardiac CT. Results: All 9 ARVC patients (100%) had epsilon waves on ECG. In PH patients, 32 and 9 patients had RV hypertrophy and fibrosis, respectively. Of these, 4 patients had both. Among 32 PH patients with RV hypertrophy, 2 had complete right bundle branch block (RBBB) and 8 had incomplete RBBB. Of 22 PH patients with RV hypertrophy but without any RBBB, two (9%, P &lt; 0.01, compared with ARVC) had waves with abnormal small upward spikes after the QRS wave. These were more marked in lead II and aVF leads than in V1 and 2 leads, and were not typical epsilon waves, suggesting RV conduction delay shown in ARVC. Fourteen patients had a negative T wave in V1-3 leads (5 had only a V1 lead, one had only V1 and 2 leads, four had only V1-3 leads, and four only had V1-4 leads, respectively). Of nine PH patients with RV hypertrophy, one had complete RBBB and one had incomplete RBBB. Of seven PH patients with RV fibrosis but without any RBBB, none (0%, P &lt; 0.01, compared with ARVC) had epsilon waves in V1-3 leads; all seven had a negative T wave in V1-3 leads (three only had a V1 lead, one had only V1 and 2 leads, two had only V1-3 leads, and one had V1-4 leads). Conclusions: In PH patients with an organized RV myocardial change, such as RV hypertrophy and/or fibrosis, the frequency of epsilon waves was significantly less than those in ARVC. Epsilon waves seem not only to be caused by an organized RV myocardium but also by other factors.
Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation
Authors: Jie Zhang, Shengwei Zhu, Ning Ma, Lee J. Johnston, Chaodong Wu, Xi Ma
Journal: Medicinal Research Reviews (2020)

In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiological defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metabolism process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are critical in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metabolism in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivatives, serotonin (5-HT) and d-tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivatives on lumen equilibrium. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.
EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity
Authors: M. K. Gandhi, T. Hoang, S. C. Law, S. Brosda, K. O’Rourke, J. W. D. Tobin, F. Vari, V. Murigneux, L. Fink, J. Gunawardana, C. Gould, H. Oey, K. Bednarska, S. Delecluse, R. U. Trappe, L. Merida de Long, M. B. Sabdia, G. Bhagat, G. Hapgood, E. Blyth, L. Clancy, J. Wight, E. Hawkes, L. M. Rimsza, A. Maguire, K. Bojarczuk, B. Chapuy, C. Keane
Journal: Blood (2020)
Abstract 237: Less is More When Using Gauze to Stop Bleeding
Authors: Nathan P Charlton, Robert Solberg, Justin Rizer, Eunice Singletary, William Woods
Journal: Circulation (2018)

Introduction: In first aid gauze is often used over the wound to absorb blood while applying pressure. Several sources recommend that if the gauze becomes saturated with blood, add more gauze and apply more pressure but offer no supporting data. However, adding more gauze will theoretically dissipate the force applied to the wound, thereby decreasing the pressure on the required area. Hypothesis: The purpose of this study is to evaluate the pressure generated when adding increasing layers of gauze to a simulated wound. Methods: In this IRB approved study subjects were recruited as a convenience sample of medical providers during a weekly medical conference. A standardized bleeding simulator (Z-Medica) and a flat (&lt;0.5 mm) force sensitive resistor were used to measure force. Subjects were randomized to order of gauze application and were instructed to apply pressure to the simulated wound with three different layers of gauze (10, 20 &amp; 30 4x4 inch cotton gauze, respectively) with the finger pads of 3 digits of the dominant hand as they would to stop bleeding. Subjects were asked to hold pressure for ten seconds and then release. All subjects completed application with each of the three stacks. Researchers were not blinded during data collection, but researchers analyzing data were blinded to the groups. Results: Thirty-three subjects were enrolled and all had data available for analysis. Twenty-two were residents, 11 attending physicians, 22 were male, and the average age of the subjects was 34.2 years (range 26-63). A steady decline in pressure with increasing amounts of gauze occurred. A stack of 10 4x4 inch gauze pads generated a constant of 3.20 (SD 1.11) lbs of force, 20 gauze pads 2.25 (SD 0.77) lbs of force, 30 gauze pads generated an average constant of only 1.5 (SD 0.54) lbs of force (p &lt;0.001). Conclusions: In this simulated model of bleeding, medical personnel generated the most force on a wound when a stack of 10 4x4 inch gauze was used to apply pressure over the wound. From this study, it is apparent that increasing the amount of gauze will decrease the amount of pressure generated on the wound. As pressure on the bleeding vessel is important in stopping bleeding, this is likely detrimental to hemorrhage control.
Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants
Authors: Jack Ansell, Bryan E. Laulicht, Sasha H. Bakhru, Allison Burnett, Xuan Jiang, Lirong Chen, Christopher Baker, Stephen Villano, Solomon Steiner
Journal: Blood (2020)
Abstract 13652: An Innate YAP/TAZ Mechanosensing Deficit in Hutchinson-Gilford Progeria Syndrome
Authors: Brandon K Walther, Anahita Mojiri, Navaneeth Krishna Rajeeva Pandian, Jacques Ohayon, Huie Wang, Jianhua Gu, Roderic I Pettigrew, Abhishek Jain, Anthony Guiseppi-Elie, John P Cooke
Journal: Circulation (2020)

Hutchinson-Gilford Progeria Syndrome (HGPS) is a disease of accelerated aging causing death in the mid-teens from myocardial infarction or stroke. The disease is caused by a point mutation in the gene encoding lamin-A. The mutated scaffolding protein is aberrantly farnesylated inducing a constellation of defects included nuclear abnormalities, genomic damage, and rapid senescence. Therapy targeting the abnormal farnesylation provides a modest extension of life, thus new insights and therapeutic approaches are urgently needed for these children. Consistent with previous morphological observations and new studies implicating YAP/TAZ mechanobiology as an important mechanical pathway for endothelial cell (EC) health under shear stress, we hypothesized that HGPS ECs have an innate mechanical disturbance rendering them unable to respond to external, atheroprotective cues. We used a microfluidic vessel-on-a-chip with channel geometries and fluid flow to precisely model the hemodynamic stimuli present in vasculature as we have previously described. We cultured iPSC-derived HGPS ECs in this system to study mechanoresponse to shear stress and YAP/TAZ signaling. HGPS ECs manifest a rounded, flattened appearance characteristic of senescent ECs, are unable to align in response to flow, and have aberrant YAP/TAZ activity despite unidirectional laminar flow. To explore the physical underpinnings of such biochemical disturbances, we used atomic force microscopy (AFM) to precisely characterize the shape of individual HGPS cells, and their deformation to a controlled force applied by the AFM cantilever. Preliminary measurements confirmed that HGPS cells have a reduced profile and are compositely stiffer (nuclear modulus + cytoskeletal modulus) than cells derived from the unaffected parent of the child. These data provide evidence of altered biophysical properties of senescent cells which we term “mechanical aging,” which is associated with aberrant signaling in response to hemodynamic stimuli. Further characterization of mechanical aging may lead to new therapeutic approaches for HGPS and other age-related diseases.
Properties of Markov Chain Monte Carlo Performance across Many Empirical Alignments
Authors: Sean M Harrington, Van Wishingrad, Robert C Thomson
Journal: Molecular Biology and Evolution (2020)

Nearly all current Bayesian phylogenetic applications rely on Markov chain Monte Carlo (MCMC) methods to approximate the posterior distribution for trees and other parameters of the model. These approximations are only reliable if Markov chains adequately converge and sample from the joint posterior distribution. Although several studies of phylogenetic MCMC convergence exist, these have focused on simulated data sets or select empirical examples. Therefore, much that is considered common knowledge about MCMC in empirical systems derives from a relatively small family of analyses under ideal conditions. To address this, we present an overview of commonly applied phylogenetic MCMC diagnostics and an assessment of patterns of these diagnostics across more than 18,000 empirical analyses. Many analyses appeared to perform well and failures in convergence were most likely to be detected using the average standard deviation of split frequencies, a diagnostic that compares topologies among independent chains. Different diagnostics yielded different information about failed convergence, demonstrating that multiple diagnostics must be employed to reliably detect problems. The number of taxa and average branch lengths in analyses have clear impacts on MCMC performance, with more taxa and shorter branches leading to more difficult convergence. We show that the usage of models that include both Γ-distributed among-site rate variation and a proportion of invariable sites is not broadly problematic for MCMC convergence but is also unnecessary. Changes to heating and the usage of model-averaged substitution models can both offer improved convergence in some cases, but neither are a panacea.
UK immigration system blamed for high level of alcohol problems among refugees
Authors: Bryan Christie
Journal: BMJ (2020)

Poverty, social isolation, and boredom among refugees and asylum seekers in the UK are major factors contributing to their abuse of alcohol, a study has found.1

The research is based on interviews with 20 refugees and asylum seekers in Scotland and the north of England and found that alcohol is used as a cheap and readily available means to cope with stress and mental ill health linked to the difficulties in dealing with the UK’s immigration system.

Although it is a small study, the authors said it provides important information on a sparsely researched topic. They …