tbuckley/cabot-search huggingface dataset:
CLINICAL CHARACTERISTICS AND OUTCOMES OF COVID-19 PATIENTS WITH AND WITHOUT PRE-EXISTING CHRONIC LIVER DISEASE
Authors: A. Krishnan, L. Prichett, X. Tao, A. Kim, A. T. Strauss, J. P. Hamilton, J. J. Potter, S. Alqahtani, T. A. Woreta, P. H. Chen
Journal: Hepatology (2020)

Background: Patients with coronavirus disease 2019 (COVID-19) often present with various degrees of liver injury Thus, patients with pre-existing chronic liver disease (LD) may be at increased risk of complications from COVID-19, but this has not yet been well characterized Aim: To examine the impact of pre-existing LD on outcomes in patients with COVID-19 Methods: In this retrospective cohort study, we analyzed data from COVID-19 patients hospitalized at the Johns Hopkins Health System between February 1, 2020, and July 1, 2020, who tested positive for COVID-19 Identified patients were then stratified into two groups based on the presence or absence of pre-existing LD The LD group consisted of patients with a diagnosis of pre-existing liver disease at the time of diagnosis of COVID-19 We studied outcomes, including the need for hemodialysis or vasopressor support, hospital length of stay (LOS), and in-hospital mortality We described categorical data as percentages, and continuous data as mean with standard error (SD) We used Pearson's chi-squared tests and analysis of variance to compare variables between the patients with and without LD Results: In a study of 2,293 patients with laboratoryconfirmed COVID-19, 129 (17 8%) patients had pre-existing LD Among them, 32 (24 8%) patients had cirrhosis;18 (14 0%) had non-alcoholic fatty liver disease;20 (15 5%) had chronic hepatitis C;5 (3 87%) had chronic hepatitis B, and 5 (3 87%) were liver transplant recipients Patients with LD were more often black (41 9%) compared to patients with no preexisting LD (35 1%, p = 0 029) LD patients had substantially higher prevalence of comorbidities, including hypertension (79 9% vs 61%, p < 0 001), diabetes (27 9% vs 15 6%, p < 0 001), chronic pulmonary disease (31 0% vs 18 4%, p < 0 0001), and anemia (43 4% vs 22%, p < 0 001) Those with LD required hemodialysis more often (10% vs 4 4%, p = 0 015) There was no difference in need for vasopressor support (20 0% vs 18 8%, p = 0 12) The hospital LOS was similar between the groups (9 5 vs 9 6 days) There was no difference in mortality between the two groups (10 0% vs 14 6%, p = 0 14) Conclusion: Patients with pre-existing LD and COVID-19 infection were more likely black, have underlying comorbidities and require hemodialysis However, they had similar hospital LOS and mortality as those without LD  These findings have important implications for patients with LD but require further validation
Abstract 14475: Successive Distal Transradial Approach for Coronary Catheterization in the Same Arm
Authors: Takeshi Yamada, Soichiro Washimi, yuki matsubara, Sho Hashimoto, Norimasa Taniguchi, Shunsuke Nakajima, Tetsuya Hata, Akihiko Takahashi
Journal: Circulation (2020)

Background: The distal transradial approach (dTRA) for coronary catheterization is a newly introduced alternative to the conventional transradial approach. This study investigated how many times the same distal radial artery can be cannulated for coronary catheterization. Methods: A total of 1717 patients underwent 2406 coronary catheterization procedures between April 2018 and March 2020. The dTRA was used as the primary approach whenever feasible in this study period, and the dTRA was used for 1555 patients (90.6%) and 2129 procedures (88.5%). Patients who underwent repeated coronary catheterization after the initial procedure using dTRA were included in this study. The incidence of successive application of dTRA in the same arm and the reasons for access site conversion were investigated. Results: A total of 430 patients were included in this study; of these, in 10 patients, the distal radial artery was cannulated on both sides in the initial procedure. The patient group included 320 men (74.4%), and the mean age was 72.2 ± 10.8 years. A 4-, 5-, or 6-French sheath or sheathless system was used in the initial procedure. A maximum of four successive coronary catheterization procedures, including the initial procedure, were carried out. The second procedure involved the distal radial artery on the same side in 394 cases (89.5%), and the fourth dTRA procedure was possible in 81.7% of the cases. Access site conversion during the follow-up procedure, which was observed in 57 cases, was attributed to radial artery occlusion (17.5%), narrowing of the distal radial artery (33.4%), tortuous route of the right upper limb approach (15.8%), and strategic reasons, such as aortography or coronary bypass graft angiography (15.8%). Conclusions: The dTRA was successfully applied in the same arm in 89.5% of the cases in the second procedure and 81.7% in the fourth coronary catheterization procedure.
HP0013 Changes in measures of pain and function in intervention studies of severe knee osteoarthritis: comparison to patient perceptions
Authors: SE Lamb, F Toye, KL Barker, S Barrington
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Questionnaires and physical performance tests are recommended for measuring changes in pain and function in knee osteoarthritis. The significance of changes in these measures is poorly understood. <h3>Aim</h3> To compare associations between patients' perceptions of change in function and pain due to a chronic disease management program, with physical performance tests and questionnaire assessments. <h3>Method</h3> The sample were 109 people being considered or waiting for knee replacement, who attended a six-week chronic disease management program. Interventions were goal setting, planning, symptom management, exercise, diet and lifestyle advice. Function and pain were assessed before and after the program by a physiotherapist, using the WOMAC,<sup>1</sup> Arthritis self-efficacy scale,<sup>2</sup> visual analogue scales (VAS) of distress and pain, timed measures of walking and sit-to-stand, and leg extensor power (LEP, Watts/Kg).<sup>3</sup> Patients gave a global assessment of change in pain and function as a result of the program as (1) much worse (2) somewhat worse (3) same (4) somewhat better (5) much better. Less than 5% of patients reported worsening symptoms, therefore categories 1–3 were combined. The mean change in outcome measures was calculated for the three levels of global patient assessments. A non-parametric ANOVA was used to test for statistically significant differences in outcomes across the three levels of global assessment, and included a test for linearity. <h3>Results</h3> The mean age of participants was 69 (SD 8.5), 44% were male, median duration of symptoms was 6 yrs (range 57.5). Over 70% of patients reported being somewhat or much better in function or pain after the program. Global ratings of pain and function demonstrated strong, linear associations with changes in WOMAC function, LEP and self-efficacy (shown for pain in the Table 1). Improvements in pain were associated with the baseline WOMAC pain score. Age, sex, and severity of disease were not associated with patients' global assessments. Neither were changes in walking speed, sit-to-stand, VAS distress, VAS pain or WOMAC pain scores. <h3>Conclusion</h3> The results suggest possible minimum clinically significant differences for use in clinical trials, and measures that reflect patient perceptions of the benefits of a chronic disease management program. <h3>References</h3> Bellamy, <i>et al</i>. 1988;15(12)1833–40 Barlow JH, <i>et al</i>. Psych Health Med. 1997;2(1):3–17 Bassey, <i>et al</i>. Eur J Appl Physiol. 1990;60(5):385–90
Abstract 14694: Coronary Artery Fistula Presenting With Complete Heart Block and Syncope
Authors: Anas Alameh, Ansaam Daoud, Ahmad Jabri
Journal: Circulation (2020)

Introduction: Coronary artery fistula (CAF) is an anomalous connection between one or more coronary arteries and a cardiac chamber or great vessel. The incidence of coronary fistulas is estimated to be 0.2-0.4% of all cardiac malformations. We present a 75 year old female who presented with a complete heart block, which was most likely caused by a fistula between the coronary vasculature and the pulmonary trunk. Clinical presentation: A 75 year old female with a past medical history of hypertension, hyperlipidemia, and COPD presented with two episodes of syncope. Clinical examination was unremarkable. The EKG showed complete third degree heart block requiring transcutaneous pacing. Echocardiography showed normal left ventricular size and function, with an ejection fraction of 55%. The right ventricle size and function were also normal. No hemodynamically significant valvular disease was seen. Left heart catheterization showed occluded middle right coronary artery, 50% stenotic lesion in the left anterior descending artery (LAD), and an abnormal termination of the first diagonal branch of the LAD (D1) into the pulmonary trunk indicative of a fistula. The fistula was the presumed cause of the complete heart block in this patient. The fistula was managed by observation rather than surgical intervention while a dual chamber pacemaker was placed to address the complete heart block. Conclusions: Coronary artery fistulas are either congenital or acquired. They are rare and usually asymptomatic but can present with a myriad of symptoms. Our case describes a patient presenting with complete heart block and syncope, with a fistula detected on coronary angiography. This is considered the gold standard for diagnosing CAF. Disrupted coronary flow leading to ischemic complete heart block is the presumed process leading to syncope in this patient. Other modalities that can assist in this diagnosis include echocardiography, computed tomography, or magnetic resonance imaging.
Abstract 16048: Placental Pathology in Pregnancies Complicated by Maternal Cardiac Disease: A Study From the Standardized Outcomes in Reproductive Cardiovascular Care (STORCC) Initiative
Authors: Fred M Wu, Bradley J Quade, Zoe J Schefter, Abigail Moses, Cara L Lachtrupp, john C markley, Kimberlee Gauvreau, Katherine E Economy, Anne M Valente
Journal: Circulation (2020)

Background: The incidence of pregnancy in women with cardiovascular disease (CVD) has increased, yet there is little known about placental pathology in these women. Objective: To describe placental pathology in pregnancies carried by women with CVD and to compare placental findings between categories of maternal CVD. Methods: We identified live births within the prospective, single-center Standardized Outcomes in Reproductive Cardiovascular Care cohort for which the placenta underwent histopathologic examination. Pathology reports were reviewed by an experienced placental pathologist (BJQ) for prespecified pathologic findings that were then compared against maternal characteristics. Results: 271 placentas (Table 1) were identified from pregnancies associated with maternal congenital heart disease (CHD) (65%), arrhythmia (16%), cardiomyopathy (8%), connective tissue disease (7%), and valvular heart disease (4%). Median maternal age at delivery was 32 years (range 19-49). Median gestational age at delivery was 39 weeks (range 25-41). Anatomic pathology, mostly in the form of small placenta by weight, was most common, affecting 43% of placentas. Vascular pathology, mostly maternal vascular malperfusion or fetal flow restriction, was seen in 41% of placentas. Infectious (acute chorioamnionitis) and inflammatory (chronic villitis) pathology was seen in 23% and 10% of placentas, respectively. Inflammatory pathology was more common in maternal CHD than in other CVD categories (14.9% vs. 2.1%, p=0.001), while anatomic, infectious, and vascular pathology were seen at similar rates across all CVD categories. Conclusion: Pregnancies among women with CVD commonly demonstrate abnormal placental findings, especially anatomic and vascular pathology. Chronic villitis was more common in women with CHD compared to other types of CVD. Otherwise, the incidence of specific pathology findings did not differ significantly based on maternal characteristics.
Abstract 15400: Impact of Human Immunodeficiency Virus Infection on Takotsubo Cardiomyopathy Outcomes in a Large Nationwide Sample
Authors: Laith Ali, Amre Ghazzal, Raja Zaghlol, Sohab Radwan, Sameer Desale, Hector M Garcia-Garcia
Journal: Circulation (2020)

Aim: Stress-Induced or Takotsubo Cardiomyopathy (TCM) is characterized by transient wall motion abnormalities often preceded by physical or emotional stress. Various baseline medical comorbidities were associated with worse outcomes theoretically due to their effect on chronic stress exposure. The effect of concurrent Human Immunodeficiency Virus (HIV) infection on outcomes of TCM has not been well established. Methods: We conducted a US-wide analysis of TCM hospitalizations from 2006 to 2014 by querying the National Inpatient Sample (NIS) database for the International Classification of Diseases-ninth Revision (ICD-9) TCM code, baseline characteristics, and inpatient outcomes. TCM patients with HIV were compared to TCM patients without HIV. Multivariate regression models were constructed to account for potential confounders. We identified 123,050 patients hospitalized with TCM, of those patients 304 had positive HIV status. Results: In unadjusted analysis (figure 1), in-hospital outcomes were worse in TCM patients with HIV in terms of development of acute kidney injury (16.8% vs 33.3%, P -value 0.002), use of invasive mechanical ventilation (18.3% vs 34.5%, P -value 0.003), and mortality (5.3% vs 17.1%, P -value &lt;0.0001). After adjusting for age, gender, and comorbidities there was no significant difference in the captured outcomes (table 1). Conclusion: TCM patient with concurrent HIV had numerically worse outcomes. After adjusting for potential confounders, the statistical significance no longer existed, suggesting that statistical difference was primarily driven by difference in baseline sociodemographic parameters and coexisting comorbidities.
Abstract 14228: Pericytes Within a Pulmonary Neurovascular Unit in Covid-19-elicited Pathologic Changes
Authors: Zhen He
Journal: Circulation (2020)

A pericyte-centered hypothesis suggests that embolisms occurring within microvasculature of a neurovascular unit can result in either parenchymal hemorrhage or intravascular congestion. Dysfunctional microvascular pericytes are featured depending on their location in the neurovascular unit. I extend the hypothesis by proposing a concept of pulmonary neurovascular unit (pNVU). In simulating pathophysiology in pulmonary embolisms, acute high-altitude illness and COVID-19, an existing local regulation of microvascular blood flow is believable. This control balances blood flow with oxygen supply to maintain physiological blood oxygen saturation level. We have reported a working module for the neurovascular unit in the sexually dimorphic nucleus of the preoptic area. Pericytes, labeled with alpha-smooth muscle actin immunoreactivity, are significantly denser within the microvasculature of the neurovascular unit in males, signifying their biological functions or potential pathophysiological role in diseases. Noticeably, an illustration provides an explanation of how malfunction of microvascular pericytes causes pulmonary focal hemorrhage, edema or microvascular congestion and thrombi [Fig. 1]. A bypass existing in the pNVU would autonomically deviate blood flow from COVID-19-affected pNVU to other healthy pNVU. Consequentially, systematically applied medicines including chloroquine and/or hydroxychloroquine became valueless due to low concentration of the medicine in the COVID-19-affected regions. Alternatively, a preventive, early antiviral therapy may be efficacious because dysfunctional blood-air exchange precedents and malfunction of pulmonary microcirculation follows. While testing the hypothesis with experimental evidence is urgently needed, supporting therapy aimed at improvement of microcirculation or rebuilding of microvascular pericytes’ physiological function may be recommended during the COVID pandemic.
Concomitant or delayed anti-TNF differentially impact on immune-related adverse events and antitumor efficacy after anti-CD40 therapy
Authors: Celia Jacoberger-Foissac, Stephen J Blake, Jing Liu, Elizabeth McDonald, Hannah Triscott, Kyohei Nakamura, Mark J Smyth, Michele WL Teng
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Concomitant tumor necrosis factor (TNF) neutralization in combination with immune checkpoint inhibitors (ICIs) reduces clinical immune-related adverse events (irAEs) and appears to improve antitumor efficacy in preclinical tumor models. Agonistic antibodies targeting costimulatory receptors such as CD40 represent an additional strategy to boost antitumor immune response and potentiate the activity of ICIs. However, the dose-limiting toxicities observed in anti-CD40-treated cancer patients have hindered its clinical development. Methods We previously described a mouse model to assess both antitumor activity and irAEs induced by various effective combination immunotherapies. Using the BALB/c and C57BL/6 strains of FoxP3-GFP-DTR (FoxP3 DTR ) mice, transient depletion of T regulatory cells (Tregs) prior to immunotherapy with additional immunomodulatory antibodies, lowered immune self-tolerance, resulting in the development of a spectrum of physical and biochemical irAEs similar to that reported clinically. In MC38 and 4T1.2 tumor models, following transient Treg depletion, we evaluated the impact of anti-CD40 on antitumor efficacy and the development of irAEs and the impact of concomitant or delayed TNF blockade on both these parameters. Physical irAEs were scored and biochemical irAEs were measured in the serum (ALT and cytokine levels). Histopathological liver and colon tissue analysis were performed to assess immune cell infiltration and tissue damage. Results Similar to early clinical trials of CD40 agonists, in our tumor models we observed liver toxicities and rapid release of proinflammatory cytokines (TNF, interleukin 6, interferon-γ). In the BALB/c strain, anti-CD40 induced severe physical and biochemical irAEs. Concomitant anti-TNF treatment abrogated weight loss, liver damage and colitis, which consequently resulted in an improved clinical score. However, concomitant anti-TNF impaired antitumor response in a proportion of anti-CD40-treated C57BL/6 FoxP3 DTR mice. Delaying TNF blockade in these mice reduced biochemical but not physical irAEs while preserving antitumor efficacy. Conclusions Our results suggest concomitant rather than delayed anti-TNF is most effective in reducing biochemical and physical irAEs induced by anti-CD40, although it had the potential to negatively impact antitumor efficacy. Furthermore, our findings highlight the utility of our mouse model to assess the severity of irAEs induced by novel immunotherapeutic agents and evaluate whether their toxicity and antitumor efficacy can be uncoupled.
Eph Receptors in the Immunosuppressive Tumor Microenvironment
Authors: Peter W. Janes, Mary E. Vail, Matthias Ernst, Andrew M. Scott
Journal: Cancer Research (2020)

The tumor microenvironment (TME) promotes tumor development via complex intercellular signaling, aiding tumor growth and suppressing immunity. Eph receptors (Eph) and their ephrin ligands control cell interactions during normal development, and reemerge in tumors and the TME, where they are implicated in invasion, metastasis, and angiogenesis. Recent studies also indicate roles for Ephs in suppressing immune responses by controlling tumor interactions with innate and adaptive immune cells within the TME. Accordingly, inhibiting these functions can promote immune response and efficacy of immune checkpoint inhibition. This research highlights Ephs as potential targets to enhance efficacy of immune-based therapies in patients with cancer.
Abstract 16738: Association Between First and Second Trimester Maternal Screening Biochemistry, Ultrasound, and Fetal Brain Growth in Presence of Fetal or Maternal Congenital Heart Disease
Authors: Aman Sharma, Emma Lewis, Gabrielle Gray, Jennifer R Maldonado, Diana L Knoedel, Colleen Lancial, Osamah Aldoss, Donna A Santillan, Prashob Porayette
Journal: Circulation (2020)

Introduction: Newer research has highlighted significant neurological impairments in children and adults with congenital heart disease (CHD). The more severe the heart defect, the higher the neurologic impairment. Pregnancies complicated by fetal or maternal CHD carry a higher risk of placental abnormalities. We studied the association between pregnancy hormonal levels and fetal head and body growth. Hypothesis: Placental dysfunction in pregnancies with fetal or maternal CHD alters pregnancy hormonal levels affecting fetal brain and somatic growth. Methods: We performed a retrospective case-control study on pregnant women (year 2010-2019) at the University of Iowa. Only women with first and/or second trimester prenatal screening (ultrasound and blood test) were included. Pregnancies with fetal chromosomal abnormalities, multiple gestation, maternal diabetes, smoking, or hypertension were excluded. Pregnancies were either healthy controls (n=36), women with CHD (MCHD; n=26), or fetus with CHD (FCHD; n=23). Pregnancy hormonal levels, ultrasound findings, and fetal/neonatal growth percentiles and/or z-scores data were analyzed. Results: Women with CHD were younger (p=0.004) with increased fetal nuchal translucency (p=0.003) compared to controls. Women in MCHD (p=0.02) and FCHD (p=0.02) group delivered earlier than controls. FCHD had significantly lower pregnancy associated plasma protein-A (PAPP-A) levels than controls (p=0.04). The groups had no difference in the second trimester fetal head circumference (HC) and femur length. FCHD group had significantly smaller HC percentile (p=0.03) and z-scores (p=0.03) at birth than controls. Both FCHD and MCHD had smaller birth weight and length compared to controls. However, only FCHD group demonstrated significantly lower HC to birth weight ratio (p=0.01). The controls had a positive correlation between human chorionic gonadotropin level and head circumference z-score at birth (r=0.34;p=0.053). Conclusions: Pregnant women with CHD have increased fetal nuchal translucency and deliver at earlier gestational age. Women with fetal CHD have smaller neonatal head and body size at birth with associated low PAPP-A level early in their pregnancy probably related to placental dysfunction.