tbuckley/cabot-search huggingface dataset:
Abstract 16010: Congestive Heart Failure and Coronavirus Disease 2019 Illness Severity
Authors: Max Ruge, Joanne Michelle D Gomez, Gatha G Nair, Setri Fugar, Jeanne du Fay de Lavallaz, nusrat jahan, Prutha Lavani, J. Allan Simmons, Anupama Rao, Karolina Marinescu, Kim A Williams, Annabelle S Volgman, Tisha Marie Suboc
Journal: Circulation (2020)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has killed hundreds of thousands worldwide. Those with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. Congestive heart failure (CHF) may lead to worsening COVID-19 symptoms. However, it is unclear if CHF is an independent risk factor for severe COVID-19 infection or if other accompanying comorbidities are responsible for the increased risk. Methods: From March to June 2020, data was obtained from adult patients diagnosed with COVID-19 infection who were admitted in the Rush University System for Health (RUSH) in Illinois. Heart failure patients, determined by ICD code assignments extracted from the electronic medical records, were identified. Multivariable logistic regression was performed between predictor variables and a composite outcome of severe infection consisting of Intensive Care Unit (ICU) admission, intubation, or in-hospital mortality. Results: In this cohort (n=1136), CHF [odds ratio (OR) 1.02] alone did not predict a more severe illness. Prior myocardial infarction [(MI), OR 3.55], history of atrial fibrillation [(AF), OR 2.14], and male sex (OR 1.55) were all significantly (p&lt;0.001) associated with more severe COVID-19 illness course when controlling for CHF (Figure 1). In the 178 CHF patients, more advanced age (68.8 years vs. 63.8 years; p&lt;0.05) and female sex (54.5% vs. 39.1%; p&lt;0.05) were associated with increased severity of illness. Conclusions: Prior MI, history of AF, and male sex predicted more severe COVID-19 illness course in our cohort, but pre-existing heart failure alone did not. However, CHF patients who are females and older in age are at risk for severe infection. These findings help clinicians identify patients with comorbidities early at risk for severe COVID-19 illness.
Human growth hormone.
Authors: J A Parsons
Journal: BMJ (1971)

successfully lay emphasis on an already well- established point-namely that a rise in Paco2 may be accompanied by a rise in serum potassium.In addition, they do well to re- mind us that respiratory compensation for metabolic acidosis may be abolished under anaesthesia.These are important points well made.However, I am fearful lest a casual reader of their paper may now think suxamethonium to be exonerated as a potential cause of hyperkalaemia in renal failure.As I believe this matter to be still sub judice, may I make the following observations.They state that in cases la, 4, 5, 6, and 9the compensation for metabolic acidosis present during spontaneous conscious breath-lUg is to a greater or lesser extent abolished
The global burden of illness of peanut allergy: A comprehensive literature review
Authors: Jay A. Lieberman, Ruchi S Gupta, Rebecca C. Knibb, Tmirah Haselkorn, Stephen Tilles, Douglas P. Mack, Guillaume Pouessel
Journal: Allergy (2020)

Abstract Peanut allergy (PA) currently affects approximately 2% of the general population of Western nations and may be increasing in prevalence. Patients with PA and their families/caregivers bear a considerable burden of self‐management to avoid accidental peanut exposure and to administer emergency medication (adrenaline) if needed. Compared with other food allergies, PA is associated with higher rates of accidental exposure, severe reactions and potentially fatal anaphylaxis. Approximately 7%–14% of patients with PA experience accidental peanut exposure annually, and one‐third to one‐half may experience anaphylaxis, although fatalities are rare. These risks impose considerably high healthcare utilization and economic costs for patients with PA and restrictions on daily activities. Measures to accommodate patients with PA are often inadequate, with inconsistent standards for food labelling and inadequate safety policies in public establishments such as restaurants and schools. Children with PA are often bullied, resulting in sadness, humiliation and anxiety. These factors cumulatively contribute to significantly reduced health‐related quality of life for patients with PA and families/caregivers. Such factors also provide essential context for risk/benefit assessments of new PA therapies. This narrative review comprehensively assessed the various factors comprising the burden of PA.
Abstract 15089: Specificity for Inflammatory Pathways and Myocardial Injury Associated With Coronary Microvascular Dysfunction in Rheumatoid Arthritis
Authors: Brittany Weber, Zeling He, Sicong Huang, Daniel H Solomon, Elena Massarotti, Charlotte Golnik, Thany Seyok, Seth Brownmiller, Laurel Martell, Leanne Barrett, Courtney Bibbo, Mary Bolster, Jorge Plutzky, Marcelo F DI CARLI, Katherine P Liao
Journal: Circulation (2020)

Background: Coronary microvascular disease (CMD) is associated with increased mortality in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD. However, it is not known whether specific inflammatory pathways implicated in RA play a stronger role than others in the pathogenesis of CMD. The objective of this study was to identify the associations between inflammatory cytokines, CMD, and resultant myocardial injury. Methods: We used baseline data from the first 53 subjects enrolled in a study of RA and CV risk (LiiRA, NCT02714881). LiiRA enrolls RA patients, age&gt;35, prior to TNF inhibitor initiation. All subjects underwent a stress myocardial perfusion PET scan to quantify coronary flow reserve (CFR). CFR is the ratio of myocardial blood flow during maximal hyperemia over that at rest. A lower CFR in the absence of obstructive coronary artery disease (CAD) is indicative of CMD. We tested the association between markers of inflammation and myocardial injury with CFR using the Spearman correlation. Results: Clinical characteristics of LiiRA subjects are shown in Table 1. Baseline cardiac risk factors were uncommon. IL-6, sTNFR2, NT-proBNP were correlated with lower CFR. However, no significant associations were observed between IL-1β, hsCRP, or hs-cTnT (Table 2). Conclusions: Among RA patients with no history of overt CAD, the severity of CMD was correlated with IL-6 and sTNFR2 but not IL-1β or hsCRP. CMD was further associated with increased levels of NT-proBNP but not hs-cTnT. These findings provide potential insight into the mechanisms by which inflammation mediates CMD and resultant myocardial dysfunction.
Abstract 17135: Promoting Early Mobility and Discharge in Patients Post-Transcatheter Aortic Valve Replacement
Authors: Lindsey Hart, Robert Frankel, Gregory Crooke, Mary Alice Moors, Stefanie Noto, Bradi B Granger
Journal: Circulation (2020)

Background: Aortic stenosis is a common disease that affects older adults. With an expanded indication, low-risk patients can now be offered the option of TAVR. Hospitals will need to effectively and efficiently accommodate the expected increase in demand for the TAVR procedure without compromising patient outcomes. Objective: The purpose of this study was to evaluate the development of a post-transcatheter aortic valve replacement protocol to standardize care and progress the patient from the operating room to discharge. Methods: We used a prospective pre-post design to evaluate the effect of education and a technology-supported intervention on length of stay, quality of life (measured by the Kansas City Cardiomyopathy Questionnaire; KCCQ12), and early mobility in TAVR patients between April 2019 and March 2020. Interventions: Two components of the intervention included team-based education and integration of guideline-based orders in the electronic record (EHR). Education regarding expectations for early mobilization and discharge plan was provided to patient and staff to ensure a timely discharge home. Results: Overall and post-procedural length of stay were significantly improved (5.26 days vs 2.45; p&lt;0.001 and 3.05 days vs 2.16 days; p&lt;0.004) respectively. Quality of life improved in both groups from baseline to 30 day follow up (p=0.012) No significant difference was shown in the 5-meter walk test. Conclusion: These findings suggest that implementation of an evidence based EHR-embedded order set is associated with a significant improvement in overall and post-procedure length of stay at 6 moths and a significant improvement in post-procedure quality of life. Future work is needed to examine strategies to ensure safe next day discharge.
Abstract 15624: The Anti-lung Cancer Drug (R)-crizotinib Predisposes and Exacerbates Pulmonary Hypertension
Authors: Charifa awada, Francois Potus, Eve Tremblay, Roxane Paulin, Steeve Provencher, Sebastien Bonnet, Olivier BOUCHERAT
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a vascular disease characterized by persistent elevation of pulmonary vascular resistance leading to right heart failure and death. In 10% of cases, PAH is induced by drugs including chemotherapeutic agents such as RTK inhibitors (e.g. dasatinib). (R)-Crizotinib is an ALK/ROS1/MET inhibitor increasingly used for the treatment of non-small cell lung cancer (NSCLC). Interestingly, (R)-Crizotinib has been shown to induce endothelial cells (EC) dysfunction and is associated with dyspnea and peripheral oedema, which are central symptoms of PAH. We thus hypothesized that chronic administration of (R)-Crizotinib exacerbates and predisposes PAH. Material and results: We found that daily administration of (R)-Crizotinib (100mg/kg for 2 weeks) in Sugen/Hypoxia (Su/Hx) PAH rat model significantly increased mortality rates. Compared to vehicle-treated rats, (R)-Crizotinib was associated with worsening of hemodynamic parameters (RVSP, mPAP, SV, CO and TPR measured by right heart catheterization; p&lt;0.05; n=4-6). Histologically, (R)-Crizotinib enhanced pulmonary arteries (PA) wall thickness (EVG stain; p&lt;0.05) and increased fibrosis and macrophages accumulation in the lungs and right ventricle. In addition, we showed that pretreatment of rats with (R)-Crizotinib exaggerates the response to monocrotaline (MCT, 40mg/kg), as revealed by histological (increase in vascular remodeling) and hemodynamic measurements (mPAP; TPR; CO) (p&lt;0.01; n=7-10). In vitro, (R)-Crizotinib reduced MET and AKT activation (WB) in human PA endothelial cells promoting endothelial dysfunction via decreased proliferation (Ki67) and increased apoptosis (Annexin V) rates. In addition, (R)-Crizotinib interferes with autophagy flux (increase in LC3-II and p62 accumulation) and was accompanied by the appearance of atypical morphological phenotypes in PA endothelial cells (multinucleated cells). Conclusion: We showed for the first time that (R)-Crizotinib treatment predisposes and exacerbates PAH in animal models (Sugen/Hypoxia and monocrotaline). Understanding the mechanism will provide promising perspectives for a better management of patients treated with (R)-Crizotinib or ALK/ROS1/MET inhibitors.
Research on research funding: an imperative for science and society
Authors: Anna Severin, Matthias Egger
Journal: British Journal of Sports Medicine (2020)

Research in medicine and public health is essential for the future well-being of society. In sports medicine, research has, for example, shown that psychological, social and contextual factors all influence recovery processes after sport-related injuries.1 Such an understanding is central to optimise rehabilitation and improve outcomes and quality of life.

Many members of the BJSM community are well versed in the research funding world. In research funding, peer review of grant applications is considered the best practice for deciding which projects or scholars are funded. There are, however, concerns about the validity of peer-review and research evaluation. A recent systematic review indicated that grant peer review in the health sciences suffers from biases, conservatism and is a weak predictor of future research performance.2 We acknowledge that maximising effectiveness and fairness of public research funding is challenging and in this editorial, we argue that research on research funding is required to reduce biases and conservatism and increase the efficiency of grant review.

There are inherent weaknesses in grant review, which raise the question if it is the best method for allocating research funding. As funding organisations only recently have begun to investigate their review processes, most evidence on these challenges is anecdotal. Additionally, not much is known …
Time is of the essence: Coupling sleep-wake and circadian neurobiology to the antidepressant effects of ketamine
Authors: S. Kohtala, O. Alitalo, M. Rosenholm, S. Rozov, T. Rantamäki
Journal: Pharmacology & Therapeutics (2020)

Several studies have demonstrated the effectiveness of ketamine in rapidly alleviating depression and suicidal ideation. Intense research efforts have been undertaken to expose the precise mechanism underlying the antidepressant action of ketamine; however, the translation of findings into new clinical treatments has been slow. This translational gap is partially explained by a lack of understanding of the function of time and circadian timing in the complex neurobiology around ketamine. Indeed, the acute pharmacological effects of a single ketamine treatment last for only a few hours, whereas the antidepressant effects peak at around 24 hours and are sustained for the following few days. Numerous studies have investigated the acute and long-lasting neurobiological changes induced by ketamine; however, the most dramatic and fundamental change that the brain undergoes each day is rarely taken into consideration. Here, we explore the link between sleep and circadian regulation and rapid-acting antidepressant effects and summarize how diverse phenomena associated with ketamine's antidepressant actions - such as cortical excitation, synaptogenesis, and involved molecular determinants - are intimately connected with the neurobiology of wake, sleep, and circadian rhythms. We review several recently proposed hypotheses about rapid antidepressant actions, which focus on sleep or circadian regulation, and discuss their implications for ongoing research. Considering these aspects may be the last piece of the puzzle necessary to gain a more comprehensive understanding of the effects of rapid-acting antidepressants on the brain.
Abstract 13880: A Novel, Evidence-based, Standardized Discharge Checklist Reduces Thirty Day Heart Failure Readmissions in an Urban Safety Net Hospital
Authors: Paul J Marano, Alexandra B Steverson, Caren Chen, Yifei Ma, Rachel J Stern, Jonathan Davis, Priscilla Hsue, Lucas S Zier
Journal: Circulation (2020)

Introduction: Safety net hospitals are more likely to be penalized for heart failure (HF) readmissions. There is limited evidence as to whether readmission reduction strategies are effective in this setting. We hypothesized that a discharge checklist would reduce readmissions in an urban safety net hospital. Methods: We implemented a novel HF discharge checklist in an academic safety net hospital in San Francisco from October 2018 to April 2019. The checklist included 1) achievement of euvolemia based on physical exam, 2) prescription of guideline-directed medical therapy, and 3) establishment of scheduled follow-up within 7 days of discharge. All HF patients who were discharged with the checklist in the 6 month study period were retrospectively compared to all HF patients discharged in the 6 months prior to the implementation of the checklist. The primary outcome was the 30-day readmission rate and multivariate modeling was used to assess the significance of each checklist component. Results: Demographics were similar between the intervention (n=118) and control (n=265) groups. Of all 383 patients, mean age was 60±13 years, 102 (27%) patients were women, 170 (44%) were black, 88 (23%) were latinx, 127 (33%) were not housed, 208 (54%) used illicit substances, and 289 (76%) had ejection fraction ≤ 40%. Use of the checklist was associated with a 13.3% absolute reduction in the 30-day readmission rate (33.6% vs 20.3%, p=0.009). The intervention group was more likely to be discharged on guideline-directed medical therapy (54% vs 25%, p&lt;0.0001) including beta blockers (89% vs 71%, p&lt;0.0001), ACEI/ARBs (88% vs 66%, p&lt;0.0001) and MRAs (50% vs 23%, p&lt;0.0001). The intervention group was also more likely to have scheduled follow-up within 7 days (70 vs 58%, p=0.02). There was no difference between the groups in achievement of euvolemia. In all patients, multivariate analysis adjusted for demographics and insurance status demonstrated that the prescription of guideline-directed medical therapy was associated with lower risk of readmission (OR 0.31, 0.15-0.64). Conclusions: A novel, inexpensive discharge checklist increased the prescription of guideline-directed medical therapy and significantly reduced 30-day HF readmissions in a safety net hospital.
Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology Platform 6-14)
Authors: Solange Peters, Enriqueta Felip, Urania Dafni, Amanda Tufman, Matthias Guckenberger, Ruth Álvarez, Ernest Nadal, Annemarie Becker, Hansjörg Vees, Miklos Pless, Alex Martinez-Marti, Maarten Lambrecht, Nicolaus Andratschke, Zoi Tsourti, Anne-Christine Piguet, Heidi Roschitzki-Voser, Adrian Gasca-Ruchti, Johan Vansteenkiste, Rolf A. Stahel, Dirk De Ruysscher
Journal: Journal of Thoracic Oncology (2020)
Alpha chain inclusions in peripheral blood erythroblasts and erythrocytes
Authors: Barbara J. Bain
Journal: American Journal of Hematology (2020)

Because of the imbalance between the rate of synthesis of α and β globin chains, α chains precipitate within erythroblasts in the bone marrow in β thalassemia intermedia and major. Sometimes they are also apparent in the peripheral blood in both erythroblasts and erythrocytes. They are particularly likely to be seen in erythrocytes if the pitting function of the spleen has been lost as a result of splenectomy. The top images (×100 objective) show the peripheral blood film of a young woman with β thalassemia major who has had a splenectomy and who, because of psychological problems, has been receiving suboptimal transfusion therapy. Her blood count showed: total nucleated cell count 185 × 109/L, WBC 7.4 × 109/L, Hb 63 g/L, MCV 68 fL, MCH 20 pg and MCHC 291 g/L. The blood film is dimorphic (post-transfusion) and in addition shows nucleated red blood cells (two with lobulated nuclei), Howell-Jolly bodies, Pappenheimer bodies and an acanthocyte. There are three erythrocytes containing α chain inclusions (arrows) [top left and right image]. The lower images are from a patient with β thalassemia intermedia (also known as non-transfusion-dependent β thalassemia) with an unusual molecular mechanism. This 10-year-old African patient had compound heterozygosity for β0 thalassemia and hereditary persistence of fetal hemoglobin (HPFH2). The blood count showed Hb 94 g/L, MCV 62 fl, MCH 18.5 pg and MCHC 297 g/L. The blood film (lower images, ×100) shows anisocytosis, poikilocytosis, hypochromic cells and Pappenheimer bodies. There are two erythroblasts, both of which contain an α chain inclusion. In the left image the cytoplasm surrounding the inclusion is packed with Pappenheimer bodies [bottom left and right image]. The presence of α chain inclusions in these thalassemic conditions provides visual evidence of severe chain imbalance, both cases having a total lack of β chain synthesis with the condition in the second patient being only partly ameliorated by increased γ chain synthesis. Nothing to report. Not applicable
Abstract 15417: Impact of Udenafil on Vascular Function in Fontan Circulation: Results From the FUEL Trial
Authors: Bryan H Goldstein, David J Goldberg, Stephen Paridon, Chen Quin Eric Lam, Gayatri Ranganathan, Emilie M Jean-st-michel, Rahul Rathod, Usha S Krishnan, Reid Chamberlain, Lanier Jackson, Adam Ware, Jon A Detterich, Salil Ginde, Peter Sassalos, Marcus S Schamberger, Christopher Petit, Shabana Shahanavaz, Olukayode D Garuba, edward j woodford, Angela Weingarten, Michele Mietus-Snyder, David A White, Michael DiMaria, Colin Conner, Jason Christensen, Michael Khoury, Ja Kyoung Yoon, Carol Prospero, victor zak, Elaine M Urbina
Journal: Circulation (2020)

Introduction: In the Pediatric Heart Network double-blind Fontan Udenafil Exercise Longitudinal (FUEL) trial, treatment with udenafil (Mezzion Pharma Co Ltd) for 6 months was associated with modest improvements in exercise capacity and ventricular performance (NCT02741115). Measures of vascular function, which have been related to Fontan exercise capacity, were also obtained but have not been explored in detail. Methods: Endothelial function (Framingham reactive hyperemia index, FRHI; area under the curve to max occlusion, AUC Max ) and arterial stiffness (augmentation index, AI) were assessed with peripheral arterial tonometry. The primary outcome was the effect of udenafil vs. placebo on vascular function. Secondary outcomes included baseline, and 26-week change from baseline, measures of vascular function in subgroups of the udenafil arm, stratified by exercise response. Exercise response was defined by longitudinal change in peak oxygen consumption and categorized by 1) any positive change vs. other and 2) tertile of change. Results: Paired measures of vascular function were analyzed in 164 (82%) and 167 (84%) udenafil and placebo participants, respectively. There were no baseline differences between groups, including the use of vasoactive medications. Overall, there were no differences in change in measures of vascular function between treatment groups. In subgroup analysis, exercise responders demonstrated better baseline endothelial function (FRHI: 0.39 ± 0.37 vs. 0.29 ± 0.31, p=0.056; AUC Max : 6.53 ± 2.91 vs. 5.63 ± 2.21, p=0.023) and suggestion of a 26-week reduction in arterial stiffness (AI: -1.42 ± 10.3 vs. 1.69 ± 11.7, p=0.075). Analysis by tertile of exercise response showed that AI was significantly improved in the top tertile of exercise responders (-3.27 ± 8.4 vs. 2.62 ± 12.4 vs. 0.35 ± 11.1, p=0.022) compared with the lower tertiles. Conclusions: In the FUEL trial, treatment with udenafil was not associated with significant changes in measures of vascular function. Udenafil-treated participants with evidence of exercise responsiveness to therapy manifest better baseline endothelial function and a significant improvement in arterial stiffness. Vascular function may play a role in PDE-5 responsiveness in Fontan circulation.