tbuckley/cabot-search huggingface dataset:
Understanding the Patient Experience Through the Lenses of Racial/Ethnic and Gender Patient-Physician Concordance
Authors: Antoinette Schoenthaler, Joseph Ravenell
Journal: JAMA Network Open (2020)

Junko Takeshita, MD, PhD, MSCE; Shiyu Wang, MS; Alison W. Loren, MD, MSCE; Nandita Mitra, PhD; Justine Shults, PhD; Daniel B. Shin, PhD; Deirdre L. Sawinski, MD
Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion–Related Events with Brolucizumab
Authors: Jordi Monés, Sunil K. Srivastava, Glenn J. Jaffe, Ramin Tadayoni, Thomas A. Albini, Peter K. Kaiser, Frank G. Holz, Jean-Francois Korobelnik, Ivana K. Kim, Christian Pruente, Timothy G. Murray, Jeffrey S. Heier
Journal: Ophthalmology (2020)

An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.
Abstract 340: Analysis of Post Cardiac Arrest Recovery Services
Authors: Nassim Stegamat, Jonathan Elmer, Clifton W Callaway, Ankur A Doshi
Journal: Circulation (2020)

Introduction: Cardiac arrest survivors may suffer sustained functional, psychiatric and cognitive impairments . Survivors’ perspectives on outpatient services necessary for recovery are unknown. Hypothesis: Survivors rate the usefulness of certain outpatient services more highly than others. Methods: We performed a structured phone interview of patients treated from 2010 to 2018 at a single center after cardiac arrest who survived at least one year. We asked survivors or their proxies about their experiences with physician, rehabilitation and care coordination services. Survivors rated usefulness of each resource on a Likert scale (1 “not useful” to 4 “essential”) and identified the single most useful resource. Results: We interviewed 25 survivors. All received outpatient physician services (24 primary care (PCP); 19 cardiologist, 7 neurologist, and 7 other). Subjects identified PCP (12/25, 48%) and cardiologist (12/25, 48%) services most useful. Seventeen (68%) subjects received outpatient rehabilitation (13 physical therapy; 9 occupational therapy; 8 speech therapy; 8 cardiac rehab; and 1 pulmonary rehab). Subjects considered physical therapy (9/17, 53%) and cardiac rehab (6/17, 35%) most useful. Nine (36%) subjects received care coordination (5 psychological; 4 case management; 3 home nursing). Median rating of usefulness for all services was 3. Only three subjects rated either cardiologist, physical therapy or psychological services as non-useful. Conclusion: Cardiac arrest survivors may require multiple and varied outpatient services. The most beneficial services include PCP, cardiologist and physical therapy. Survivors vary in their needs, and care should be tailored to the individual.
Complications in Patients With COVID-19
Authors: Matthieu Legrand
Journal: JAMA Cardiology (2020)

Complications in Patients With COVID-19To the Editor Madjid et al 1 recently reviewed the association between the cardiovascular system and infection with coronavirus disease 2019 (COVID-19).They point out the association between cardiovascular risk factors and the outcome of patients with COVID-19.However, the underlying risk associated with obesity was not listed among the risk factors.There are several lines of evidence that being overweight or obese is associated with risk of poor outcome (ie, admission to an intensive care unit or death) after infection with COVID-19.Recently, 72% of 775 patients with COVID-19 admitted to an intensive care unit in the UK were reported to have a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) greater than 25 and 38% had a BMI greater than 30, 2 a proportion higher than in the standard intensive care population.Obesity is also reported as a risk factor of poor outcome by the US Centers for Disease Control and Prevention. 3 A potential pathophysiological background exists linking the increasing severity of COVID-19 among patients with obesity.COVID-19 binds to angiotensin-converting enzyme 2 (ACE2), a surface molecule that allow the virus to enter the host cell.In this line, the role of angiotensin-conversing enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in the pathogenicity of COVID-19 has been intensively debated. 4The level of ACE2 expression has been reported to be high in adipose tissue, therefore likely making the adipose tissue a reservoir for severe acute respiratory syndrome coronavirus 2. 5 In turn, the adipose tissue can trigger an increased inflammatory response to infection, potentially affecting all organs.Finally, patients with obesity can be at higher risk of hypoxemia due to altered thoracic compliance and the risk of lung atelectasis.I suggest that both BMI and treatment with ACEi or ARB be systematically reported in case series of patients with COVID-19 to further appreciate their interaction and association with outcome.Further research should then explore the impact of adipose tissue on the viral load, the systemic inflammatory response, and the outcome of patients with COVID-19.In the meantime, the potential risk of future deterioration should probably be appreciated in overweight patients developing COVID-19-related symptoms.
Abstract 14358: Treadmill Exercise Testing Improves Diagnostic Accuracy in Children With Concealed Congenital Long QT Syndrome
Authors: Trisha Patel, Stanley Kamande, Elizabeth Jarosz, James Bost, Sridhar hanumanthaiah, Charles I Berul, Elizabeth D Sherwin, Jeffrey P Moak
Journal: Circulation (2020)

Introduction: Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve as a guide for which children with borderline prolonged QT intervals may be gene positive for LQTS. Methods: Pediatric patients (n=139) were divided into three groups: Controls (n=76), gene positive LQTS with borderline QTc (n=21), and gene negative patients with borderline QTc (n=42). Borderline QTc was defined between 440 to 470 (male) and 440 to 480 (female) msec. ECGs were recorded while supine, sitting, and standing. Patients then underwent treadmill stress testing using the Bruce protocol followed by a 9-minute recovery phase. Statistical analysis was completed to compare the QTc intervals amongst all three of the groups using t-test, ANOVA, and the Youden method to calculate sensitivity and specificity cut points. Results: Supine resting QTc, age, and Schwartz score for the three groups were: 1) Gene positive: 446 ± 23 msec, 12.4 ± 3.4 yo, 3.2 ± 1.8; 2) Gene negative: 445 ± 20 msec, 12.1 ± 2.8 yo, 2.0 ± 1.2; and 3) Control: 400 ± 24 msec, 15.0 ± 3 yo. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at six minutes. Standing QTc ≥ 460 msec differentiated borderline prolonged QTc patients (Gene positive and Gene negative) from controls with a specificity of 90% for gene positive versus control and 83% for gene negative versus control. A late recovery QTc ≥ 480 msec at minute six distinguished Gene positive from Gene negative patients with a specificity of &gt;97%. Conclusions: Exercise stress testing can be useful to identify Gene positive borderline LQTS from a normal population and Gene negative borderline QTc patients, allowing for increased cost effectiveness by selectively gene testing a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.
Abstract IA-05: Immune health and intratumoral immune heterogeneity: Barriers to the efficacy of immunotherapy in pancreatic cancer
Authors: Gregory Beatty
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) has shown remarkable resistance to immunotherapy including immune checkpoint blockade, vaccines, and other immunomodulatory agents. In cancer, immunosurveillance can be regulated at both the priming and effector phases of an immune response. Based on this reasoning, we investigated a role for the CD40 pathway in mice and humans as a strategy to prime for tumor-reactive T cells. Our studies showed that systemic CD40 activation triggers productive innate immunosurveillance that sensitizes PDAC tumors to chemotherapy but is insufficient to provoke T cell dependent anti-tumor immunity. However, CD40 activation can restore the functional capacity of peritumoral T cells. Consistent with this, PDAC development associates with progressive loss in T cell priming capacity along with a deficiency in circulating dendritic cells. This biology observed in mouse models is mirrored in humans where patients with PDAC show a decrease in circulating dendritic cells and an increase in T cell dysfunction. To overcome these defects in T cell priming and deficiencies in immune health, we studied adoptive transfer of tumor-reactive chimeric antigen receptor (CAR)-modified autologous T cells in patients. Our findings show that the persistence of adoptively transferred T cells is markedly impaired in patients with PDAC compared to hematologic malignancies. In addition, CAR-T cells show limited anti-tumor activity in PDAC. This lack of efficacy has prompted our investigation into the biology of the tumor microenvironment which displays remarkable spatial heterogeneity in immune cell infiltrates. In our studies, we have identified phenotypically distinct cellular communities marked by weak (“cold”) and strong (“hot”) infiltration of T cells. We find that these distinct regions of PDAC tumors are orchestrated by unique immunoregulatory mechanisms with therapeutic implications. Overall, our findings demonstrate that immunological barriers residing both within and outside the tumor microenvironment have the potential to impair the efficacy of immunotherapy in PDAC. In addition, our data suggest that the immunogenicity of PDAC varies spatially throughout tumors raising the likelihood that multiple, distinct mechanisms of immune evasion will need to be circumvented for immunotherapy to produce benefit for most patients. Citation Format: Gregory Beatty. Immune health and intratumoral immune heterogeneity: Barriers to the efficacy of immunotherapy in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-05.
Abstract 13937: QT Monitoring in Early Stage Asymptomatic/Paucisymptomatic Covid-19 Subjects on Hydroxychloroquine/Azithromycin Off-label Regimen - <i>Iwatch</i> ECG
Authors: Antonella Sabatini
Journal: Circulation (2020)

Introduction: Covid-19 has disrupted our quality of life worldwide. Among off-label therapeutic approaches for early stage non-hospitalized asymptomatic/paucisymptomatic COVID-19 subjects, the use of hydroxychloroquine (HCQ)/azithromycin (AZM) regimen is currently widely used in Italy. One concern is how to easily evaluate cardiac toxicity by monitoring ECG QT-interval at base and during follow-up. Purpose: The purpose of this work is to illustrate a validation method by comparing a 12-lead ECG and the simultaneous Apple iWatch Lead-I ECG function for QT monitoring. Methods: 2 asymptomatic subjects underwent 2 ECGs: • The 12-lead and the Apple iWatch Lead-I ECGs were read and QT evaluated: • QT-segments were scanned and digitized by DigitizeIt (www.digitizeit.de, ver. 2.2.2) • Pearson correlation coefficient was calculated (12-lead ECG QT-segment and Apple iWatch Lead-I ECG function QT-segment). • Comparison of QT-segments and correlation coefficient of the QT-segments in the 12-ECG and the Apple iWatch Lead-I ECG function are in Table. Results: Table. Conclusions: Based on our data: 1. Pearson Correlation Coefficient (R) reflects the correlation of the QT-segments of the ECGs performed by the Apple iWatch Lead-I ECG function and the 12-Lead ECG in the male subject (R=0.8). 2. The coefficient R reflects poor correlation, hence indicating the 2-hours difference and different conditions in the female subject 2 ECGs (R= -0.03). 3. QT-segment evaluation obtained by the Apple iWatch Lead-I ECG function approaches the value of the QT-segment obtained by the 12-lead ECG machine. Hence, considering the emergency situation produced by COVID-19, and assuming still critically difficult situations in the various health systems globally, clinicians using off-label hydroxychloroquine/azithromycin regimen for asymptomatic/paucisymptomatic early stage COVID-19 subjects may find appropriate to monitor cardiac toxicity risks by Apple iWatch Lead-I ECG function.
Abstract 16313: Islands of Organized 1:1 Conduction Within Atrial Fibrillation as Potential Targets for Ablation
Authors: Prasanth Ganesan, Neal K Bhatia, Albert J Rogers, David E Krummen, Mahmood Alhusseini, Paul Clopton, Wouter-Jan Rappel, Sanjiv M Narayan
Journal: Circulation (2020)

Introduction: Organized regions in atrial fibrillation (AF) substrate are well known, but how they are defined and if they can be used to improve ablation are unclear. We hypothesized that large islands of 1:1 electrogram (EGM) propagation (i.e. ‘atrial tachycardias’) within AF may serve as effective ablation targets. Methods: We recruited 40 persistent AF patients at ablation (age 54.5 ± 5.1 years). Group 1 had acute AF termination during ablation (n=20) and Group 2 did not (n=20). Basket catheters (64 poles) were placed in both atria and unipolar EGMs were analyzed to identify islands from vector contours (Wavefront Field, WFF, fig A, left) and if electrograms have 1:1 activation on classical analysis (fig A, right). Results: Organized islands of 1:1 EGM within AF were identified by vector analysis of panoramic maps, in 100% of Group 1 and 75% of Group 2 patients (p&lt;0.01). Sites lay outside PVs in both Group 1 (70%) and Group 2 (95%). Organized 1:1 island sites controlled larger areas prior to termination in Group 1 than prior to cardioversion in Group 2 (44.1 ±11.1% vs. 16.6 ± 6.9% mapped atrium, p&lt;0.0001, fig B). In Group 1, sites of AF termination had larger organized islands than competing sites (22.4 ± 7.0%; P &lt; 0.01). Conclusions: We demonstrate organized of 1:1 electrograms in AF, akin to ‘atrial tachycardia’. Islands were larger in patients with AF termination, and at their ultimate termination sites than at random sites or patients without AF termination. Future studies should identify mechanisms for organized islands.
Abstract 14455: Hidden in Plain Sight: An Elusive Cause of Cardiogenic Shock
Authors: Sarah Chuzi, Anjan Tibrewala, Fei Li Kuang, Benjamin Freed, Esther Vorovich, Jon W Lomasney, Karlyn Martin, Sadiya S Khan
Journal: Circulation (2020)

A 54-year-old man with chronic obstructive pulmonary disease (COPD) presented with three days of chest pain, dyspnea on exertion, and orthopnea. Physical examination revealed jugular venous distention and lower extremity edema. Cardiac biomarkers were elevated. The differential diagnosis for the clinical presentation included: acute coronary syndrome, and type II myocardial infarction or myocardial injury due to acute decompensated heart failure. External records demonstrated recurrent admissions for similar signs and symptoms, with negative coronary angiogram. Shortly after admission, the patient developed acute cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. Echocardiogram revealed biventricular failure and a possible mitral valve vegetation. The differential diagnosis was refined to include myocarditis (infectious and noninfectious causes), bacterial versus marantic endocarditis, and infiltrative cardiomyopathies. Transesophageal echocardiography revealed mass-like, bileaflet thickening of the mitral valve, not consistent with true vegetation. Infectious, rheumatologic, and hypercoagulable workups were negative. Given the lack of a unifying diagnosis, a right ventricular (RV) endomyocardial biopsy was pursued. This revealed myocardial necrosis and fibrosis, and a mural thrombus with extensive eosinophils. The primary data was then revisited, which revealed history of peripheral eosinophilia that was intermittently suppressed by steroids given for COPD. Cardiac magnetic resonance imaging (MRI) demonstrated diffuse biventricular subendocardial late gadolinium enhancement and RV thrombi. Evaluation for underlying causes of eosinophilia was negative leading to the diagnosis of Loeffler’s endocarditis due to idiopathic hypereosinophilic syndrome. This case demonstrates: (1) the important role of cardiac MRI in the evaluation of both unexplained myocardial injury and new cardiomyopathy, (2) a rare case of Loeffler’s endocarditis requiring mechanical circulatory support, and (3) the consequences of both availability bias and failure to fully “unpack” the primary diagnostic data, which rendered the true etiology of the patient’s cardiogenic shock “hidden in plain sight.”
Abstract 14921: Sulfated Dextran-coated Iron Oxide Nanoparticles Detect Inflammation in the Acute Phase of Myocardialsulfated Dextran-coated Iron Oxide Nanoparticles Detect Inflammation in the Acute Phase of Myocardial Infarction
Authors: Yuko Tada, Gentaro Ikeda, Angelique Louie, Phillip Yang
Journal: Circulation (2020)

Introduction: We investigated whether the negatively-charged sulfated dextran-coated iron oxide (SDIO) nanoparticles with higher affinity with macrophage can delineate inflammation more efficiently compared to non-sulfated dextran-coated iron oxide (DIO) nanoparticles in mice LAD ligation model. Methods: After mice were induced with LAD ligation, SDIO or DIO nanoparticles (15mg/kg) were injected intravenously at either day 1, day 3, day 5, and day 7. MRI was performed pre- and post-24 hours later. Dephasing signal loss caused by iron-oxide nanoparticles was detected by gradient echo sequence. Iron uptake was quantified by T2* mapping and calculated as delta R2* (=1/T2*(post)-1/T2*(post)) in the region of interest in the infarct, peri-infarct, and remote zones. Results: SDIO injection produced clear signal voids in the peri-infarct zone at day 3 (n=8), which extend into the infarct zone at day 5 (n=3) (figure). The signal was remarkably decreased at day 7 (n=7). Iron uptake represented by delta R2* in the peri-infarct (80.6±35.7 s -1 ) was significantly higher than that in the infarct (32.3±32.6 s -1 , p&lt;0.001) and the remote (5.1±16.7 s -1 , p&lt;0.0001) at day 3. At day 5, delta R2* in the infarct (91.6±5.4 s -1 , p&lt;0.001) and the peri-infarct (41.0±33.3 s -1 ,p=0.04) were significantly higher than the remote (4.2±14.1 s -1 , p&lt;0.001). DIO did not produce significant change in delta R2* in the peri-infarct or infarct at each time phase. The MRI signals of SDIO corresponded with the area of enhanced vascular permeability peaking at day 3-5, which precedes the macrophage infiltration. Conclusions: SDIO can detect inflammation in the peri-infarct region in the early phase of acute myocardial infarction.
Brief Online Cognitive Behavioural Intervention for Dysfunctional Worry Related to the COVID-19 Pandemic: A Randomised Controlled Trial
Authors: Tove Wahlund, David Mataix-Cols, Klara Olofsdotter Lauri, Elles de Schipper, Brjánn Ljótsson, Kristina Aspvall, Erik Andersson
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Worries about the immediate and long-term consequences of the COVID-19 pandemic may for some individuals develop into pervasive worry that is disproportionate in its intensity or duration and significantly interferes with everyday life. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The aim of this study was to investigate if a brief self-guided, online psychological intervention can reduce the degree of dysfunctional worry related to the COVID-19 pandemic and associated symptoms. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; 670 adults from the Swedish general population reporting daily uncontrollable worry about CO­VID-19 and its possible consequences (e.g., illness, death, the economy, one’s family) were randomised (1:1 ratio) to a 3-week self-guided, online cognitive behavioural intervention targeting dysfunctional COVID-19 worry and associated symptoms, or a waiting list of equal duration. The primary outcome measure was a COVID-19 adapted version of the Generalised Anxiety Disorder 7-item scale administered at baseline and weeks 1–3 (primary endpoint). Follow-up assessments were conducted 1 month after treatment completion. The trial was registered on ClinicalTrials.gov (NCT04341922) before inclusion of the first participant. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The main pre-specified intention-to-treat analysis indicated significant reductions in COVID-19-related worry for the intervention group compared to the waiting list (β = 1.14, &lt;i&gt;Z&lt;/i&gt; = 9.27, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001), corresponding to a medium effect size (bootstrapped &lt;i&gt;d&lt;/i&gt; = 0.74 [95% CI: 0.58–0.90]). Improvements were also seen on all secondary measures, including mood, daily functioning, insomnia, and intolerance of uncertainty. Participant satisfaction was high. No serious adverse events were recorded. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; A brief digital and easily scalable self-guided psychological intervention can significantly reduce dysfunctional worry and associated behavioural symptoms related to the COVID-19 pandemic.
Clinically established biodegradable long acting injectables: An industry perspective
Authors: Christian Isalomboto Nkanga, Andreas Fisch, Mazda Rad-Malekshahi, Marieta Duvnjak Romic, Birgit Kittel, Thomas Ullrich, Jing Wang, Rui Werner Maçedo Krause, Sabine Adler, Twan Lammers, Wim E. Hennink, Farshad Ramazani
Journal: Advanced Drug Delivery Reviews (2020)