tbuckley/cabot-search huggingface dataset:
Abstract 15897: Patient Experience With Telemedicine in Adults With Congenital Heart Disease
Authors: Anudeep Dodeja, Matt Granger, Deboarah Mitchell, Rosemary Chumita, tracey sisk, Curt Daniels, Saurabh Rajpal
Journal: Circulation (2020)

Introduction: COVID19 pandemic has resulted in drastic changes in healthcare delivery with increase in use of telemedicine. There is limited data on patient experience with telemedicine in adults with congenital heart disease (ACHD). Hypothesis: We hypothesized that ACHD patients would prefer in-person clinic visits over telemedicine, and this would be especially true for patients &gt; 65 years who may be at a higher risk of experiencing technical limitations. Methods: We conducted a nurse administered telephone survey (Figure 1A) based on Agency for Healthcare Research and Quality recommendations to assess patient experience after ACHD telemedicine visits from March 2020 to June 2020. Results: Of 216 patients who had ACHD telemedicine visits, 136 (63%) agreed to participate in the survey. Mean age was 45 + 18 years, majority (65%) being video encounters. Most (98%) said that the telemedicine visit was successful in addressing their healthcare needs. Only 21 (15%) patients reported technical issues. Most patients (76%) were likely to choose telemedicine in the future instead of an in-person clinic visit provided testing was done separately. Given a choice between in-person clinic visit and telemedicine: 103 (76%) preferred telemedicine, 25 (18%) preferred in-person clinic visits, and 8 (6%) had no preference (Figure1B). Of the 25 patients over 65 years, 19 (76%) would choose telemedicine over the in-person clinic, and only one patient reported technical difficulties. Conclusion: In conclusion, patients reported a positive experience with ACHD telemedicine, which was true even among elderly patients. Technical limitations were infrequent even amongst the elderly. Majority of patients felt that their healthcare needs were addressed and would consider telemedicine over clinic visits if given a choice. This data is vital as payors move away from supporting telemedicine and hospitals restructure, with and without ongoing COVID 19 concerns.
Novel dendritic polyglycerol-conjugated, mesoporous silica-based targeting nanocarriers for co-delivery of doxorubicin and tariquidar to overcome multidrug resistance in breast cancer stem cells
Authors: Yuanwei Pan, Suqiong Zhou, Yan Li, Badri Parshad, Wenzhong Li, Rainer Haag
Journal: Journal of Controlled Release (2020)
Senescent T Cells as a Resistance Mechanism to Lung Cancer Immunotherapy
Authors: Diego Salas-Benito, Iñaki Eguren-Santamaria, Miguel F. Sanmamed
Journal: Clinical Cancer Research (2020)

It has been reported that a group of patients with advanced non-small cell lung cancer showed circulating T cells with a senescent phenotype, and an abundance of such cells is associated with worse clinical response to immune checkpoint inhibitors. This study encourages further analysis of the role of senescent T cells in resistance to lung cancer immunotherapy.See related article by Ferrara et al., p. 492.
Abstract 14062: Accuracy of Exercise Induced St- Elevation in Lead Avr in the Diagnosis of Significant Left Main or Proximal Left Anterior Descending Artery Stenosis: A Systematic Review
Authors: Kirtipal S Bhatia, Subrat Das, Nirupama Krishnamurthi, Devika Aggarwal, vardhmaan jain, Bharat Narasimhan, Lily Martin, Aditya Joshi, Nina Kukar
Journal: Circulation (2020)

Introduction: ST-segment changes during exercise stress testing are diagnostic of myocardial ischemia in patients with suspected coronary artery disease (CAD). Recent studies have shown that exercise-induced ST-elevation in aVR is associated with significant stenosis of the left main (LM) and proximal left anterior descending (pLAD) arteries Methods: Search of electronic databases (Embase, Medline, and Web of Science) using MeSH terms and keywords for exercise stress test, lead aVR and CAD was performed from inception through December 2019. 2 reviewers independently screened results in 2 stages: title/abstract followed by full text. Included studies had adult patients who underwent exercise stress testing and reported the performance of ST-elevation &gt;1 mm in lead aVR for diagnosing significant LM or pLAD disease. Significant disease was defined as luminal narrowing &gt;50% and &gt;70% for LM and pLAD respectively. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios were calculated using a bivariate model, and a summary receiver operator curve (SROC) was constructed. Results: We included 6 studies with 1128 patients. The pooled sensitivity was 0.8 (95% CI 0.36-0.97; I 2 =94.7) and pooled specificity was 0.78 (95% CI 0.56-0.90; I 2 =97.8). Overall calculated positive LR was 3.56 (95% CI 2.34-5.4) and negative LR was 0.26 (95% CI 0.07-1.01). The pooled diagnostic odds ratio was 13.5 (95% CI 4.8-38.5). Hierarchical SROC curve showed an area under the curve of 0.84 (95% CI 0.81-0.87) (Figure 1). Conclusions: Our analysis showed moderate sensitivity and specificity of exercise-induced aVR ST-elevation for diagnosing significant LM or pLAD disease. The heterogeneity among studies was high, likely due to differences in patient selection. In conclusion, ST-elevation in aVR during exercise stress test increases the likelihood of having LM or pLAD disease. Large studies are needed to substantiate this finding.
Abstract 12896: Safety of Transition From Tafamidis Meglumine 20 Mg to Tafamidis Free Acid 61 Mg in Patients With Transthyretin Amyloid Cardiomyopathy
Authors: Thibaud Damy, Nowell Fine, Balarama Gundapaneni, Marla B Sultan, Martha Grogan
Journal: Circulation (2020)

Introduction: Tafamidis meglumine, available as 20 mg capsules, is approved in &gt;40 countries for use in early stage, symptomatic transthyretin amyloidosis with polyneuropathy. It is also approved in a growing number of countries as an 80 mg daily dose (4 x 20 mg capsules) and as tafamidis free acid 61 mg (a single dose bioequivalent to tafamidis meglumine 80 mg) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). As some patients receiving tafamidis meglumine 20 mg may benefit from transition to tafamidis free acid 61 mg, we assessed the hypothesis that this transition is not associated with any new safety concerns. Methods: In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) patients with ATTR-CM were treated with tafamidis meglumine 20 mg, 80 mg, or placebo for up to 30 months. Patients completing the trial could enroll in a long-term extension study (LTE) with placebo-treated patients randomized to tafamidis meglumine 20 mg or 80 mg. All patients in the LTE were later transitioned to tafamidis free acid 61 mg. Adverse events (AEs) emerging during the LTE were assessed in patients treated with tafamidis meglumine 20 mg in the LTE who transitioned to tafamidis free acid 61 mg (median exposure 19.8 months). AEs were compared with those emerging during ATTR-ACT in patients treated with tafamidis meglumine 20 mg (median exposure 29.7 months). Results: The 87 patients treated with tafamidis meglumine 20 mg in the LTE who transitioned to tafamidis free acid 61 mg had a similar incidence of the most common AEs by system organ class, and of specific AEs, as those treated with tafamidis meglumine 20 mg in ATTR-ACT (see Table ). The safety profile of tafamidis meglumine 20 mg was previously shown to be similar to placebo. Conclusions: While the duration of exposure to tafamidis free acid 61 mg was shorter than for tafamidis meglumine 20 mg, these data demonstrate that the transition to tafamidis free acid 61 mg is not associated with any new safety concerns.
Abstract 14388: Aortic Pulsatility Index Strongly Predicts Clinical Outcomes in Heart Failure Patients: A Sub-analysis of the Escape Trial
Authors: Mark N Belkin, Francis J Alenghat, Stephanie Besser, Ann Nguyen, Bow Chung, Bryan Smith, Sara Kalantari, Nitasha Sarswat, John Blair, Gene H Kim, Jonathan Grinstein
Journal: Circulation (2020)

Introduction: Aortic pulsatility index (API), calculated as (systolic - diastolic blood pressure)/pulmonary capillary wedge pressure, is a novel hemodynamic measurement representing cardiac filling pressures and contractility. Hypothesis: API would better predict clinical outcomes than traditional hemodynamic metrics of cardiac function in decompensated heart failure patients. Methods: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. API, cardiac power output (CPO), Fick cardiac index (CI), and pulmonary artery pulsatility index (PAPI) were calculated after final hemodynamic-monitored optimization. The primary outcome, assessed by univariable analysis, was combined death or need for heart transplant or left ventricular assist device at six months. Receiver operator characteristic (ROC) analyses were used to determine the cutoff value, from which Kaplan-Meier (KM) curves were constructed. Results: A total of 433 patients were enrolled in the ESCAPE trial, of which 155 had accurate final hemodynamic data. Of these, 45 (29%) experienced the primary outcome. Final API measurements predicted the primary outcome, OR 0.45 (95% CI 0.30-0.70, p&lt;0.001), while CI, CPO, and PAPI did not. ROC analyses of final advanced hemodynamic measurements indicated API best predicted the primary outcome with a cutoff (sensitivity, specificity, correctly classified, AUC) of 2.9 (76.2%, 55.3%, 61.4%, 0.71), compared to CPO 0.69 (57.8%, 57.8%, 57.4%, 0.57), CI 2.2 (50.0%, 48.2%, 48.7%, 0.52), and PAPI 2.6 (60.5%, 64.5%, 63.3%, 0.64). KM analyses indicated API (83.5% vs 58.4%, p=0.001) and PAPI (78.3% vs 59.0%, p=0.03) were predictive of freedom from the primary outcome, but not CPO or CI. Conclusions: The novel hemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared to traditional invasive hemodynamic metrics of cardiac function.
Abstract 14551: Biomarkers Predicting the Treatment-Resistant Kawasaki Disease
Authors: Yukako Yoshikane, Ryuji Fukazawa, Kyoko Imanaka-yoshida, Naho Kobayashi, Yasuhiro Katsube
Journal: Circulation (2020)

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG), plus steroids if needed, is the most effective therapy for the acute phase of KD. However, there are some very severe cases who need several times additional treatments and are at risk for CALs. In Japan, there are some scoring systems that initially predict IVIG-resistant patients. However, the problem is that these scoring systems fail in multiethnic populations. The aim of this study is to find universal biomarkers that predict treatment-resistant cases of KD. Methods: The subject was 276 KD patients, including Group 1 (n=214) who needed only 1 st line treatment, Group 2 (n=48) who needed 2 nd line treatment, Group 3 (n=14) who needed 3 rd line treatment or more. Tenascin C (TN-C), Pentraxin 3 (PTX3) and Procalcitonin (PCT) values, which were selected by systematic review, were measured before initial treatment in each group. Results: TN-C; 99.8±41.05 ng/ml in Group 1, 118.0±71.4 ng/ml in Group 2 and 183.0±25.0 ng/ml in Group 3. The TN-C level of Group 3 was significantly higher than that of all the others (p&lt;0.01). The cutoff value for distinguishing Group 3 was 142.0 ng/ml (Area under the Curve (AUC)=0.81). PTX3; 16.2±9.0 ng/ml in Group 1, 31.4±19.7 ng/ml in Group 2 and 58.0±33.0 ng/ml in Group 3. The PTX3 level of Group 3 was significantly higher than that of all the others (p&lt;0.01). The cutoff value for distinguishing Group 3 was 35.1 ng/ml (AUC=0.86). PCT; 0.79±0.77 ng/ml in Group 1, 2.55±3.01 ng/ml in Group 2 and 4.15±4.49 ng/ml in Group 3. The PCT level of Group 3 was significantly higher than that of all the others (p&lt;0.01). The cutoff value for distinguishing Group 3 was 2.55 ng/ml (AUC=0.88). When those three biomarkers combined, Group 3 can be predicted with the sensitivity 79%, the specificity 96%, the positive predictive value 50% and the negative predictive value 99%. Conclusions: It may be possible to predict treatment-resistant KD cases with high sensitivity and specificity by combining the measurement from the universal biomarkers, TN-C, PTX3 and PCT, before initial treatment.
Extracellular traps released by antimicrobial TH17 cells contribute to host defense
Authors: George W. Agak, Alice Mouton, Rosane M.B. Teles, Thomas Weston, Marco Morselli, Priscila R. Andrade, Matteo Pellegrini, Robert L. Modlin
Journal: Journal of Clinical Investigation (2020)

TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of TH17 cells that contribute to host defense against infection are not clear. To elucidate the antimicrobial machinery of the TH17 subset, we studied the response to Cutibacterium acnes, a skin commensal that is resistant to IL-26, the only known TH17-secreted protein with direct antimicrobial activity. We generated C. acnes–specific antimicrobial TH17 clones (AMTH17) with varying antimicrobial activity against C. acnes, which we correlated by RNA sequencing to the expression of transcripts encoding proteins that contribute to antimicrobial activity. Additionally, we validated that AMTH17-mediated killing of C. acnes and bacterial pathogens was dependent on the secretion of granulysin, granzyme B, perforin, and histone H2B. We found that AMTH17 cells can release fibrous structures composed of DNA decorated with histone H2B that entangle C. acnes that we call T cell extracellular traps (TETs). Within acne lesions, H2B and IL-17 colocalized in CD4+ T cells, in proximity to TETs in the extracellular space composed of DNA decorated with H2B. This study identifies a functionally distinct subpopulation of TH17 cells with an ability to form TETs containing secreted antimicrobial proteins that capture and kill bacteria.
Abstract
Journal: Allergy (2020)

Background:

Food intake in early life plays an important role in providing nutrients and setting the child up for lifelong eating habits. One aspect of early‐life foods that has been ignored is the role of the pH, on the development of oesophageal inflammation. The acidic environment within the oesophageal lumen has been linked to oesophageal inflammation and barrier injury, relating to oesophageal diseases such as EoE and GORD. We noticed an increase in the incidence of both EoE and GORD alongside an increase in the sales of infant/toddler foods, commonly containing fruit or citric acids to create a preservative free option.

Method:

We measured the pH of commercially available infant/toddler/toddler foods; pouches, infant/toddler jars and infant formula and compared to home‐made foods. We considered a pH of <4 as likely to cause oesophageal/epithelial damage.

Results:

29 of 60 tested commercially available infant and toddler feeds and bottles in Australian supermarkets were found to have a pH less than 4. This was infrequent with home‐prepared foods where the pH was less than 4 in 2 of the 8 foods. In particular, products containing apple puree and citric acid were acidification factors.

Conclusion:

Many commercially available infant/toddler foods have the capacity to induce epithelial injury due to its low pH. This has implications that require further investigation for the pathogenesis and also for the prevention and treatment of oesophageal diseases. Epithelial barrier integrity and inflammation has become a recent focus in the aetiology of allergic diseases; which are also dramatically increasing in the last few decades.
Abstract 14590: Cardiac Rehabilitation Utilization After Percutaneous Coronary Intervention Remains Exceedingly Low and is Strongly Associated With the Treating Hospital and Operator: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Devraj Sukul, Milan Seth, Michael Thompson, Steven J KETEYIAN, Thomas F Boyden, Jessica Yaser, John Syrjamaki, Hitinder S Gurm
Journal: Circulation (2020)

Introduction: Despite its proven benefits, cardiac rehabilitation (CR) use remains low. Identifying the sources of variation in CR referral and downstream use may help direct policies and quality improvement efforts. Objectives: We sought to quantify the magnitude of hospital and operator-level variation in CR referral and utilization after percutaneous coronary intervention (PCI). Methods: We used clinical registry data from patients (pts) discharged after PCI between 1/2012 and 10/2016 at 32 Michigan hospitals performing at least 100 PCIs linked to Blue Cross Blue Shield or Medicare claims. Registry and claims data were used to identify (i) CR referral prior to discharge and (ii) any CR use within 90 days after discharge. We calculated hospital-level risk and reliability adjusted rates of CR referral and utilization with Bayesian hierarchical regression models adjusted for patient characteristics and clustering by hospital and operator. Median odds ratios (MORs) with 95% credible intervals (CI) measured variation attributable to hospitals and operators. Results: Among 33,593 pts with a valid zip code and discharged home after PCI, 76.4% received an in-hospital referral for CR. Overall CR use was 26.7% and 31.3% among those who received an in-hospital referral. Adjusted rates of CR referral and use across hospitals ranged from 1.0%-100% and 14.9%-73.9%, respectively (Fig). After adjusting for pt factors, there was significant hospital and operator-level variation in CR referral with MORs of 5.91 (95% CI 4.02-9.34) and 1.71 (95% CI 1.60-1.85), respectively. There was also significant hospital and operator-level variation in CR use with MORs of 1.99 (95% CI 1.67 - 2.46) and 1.36 (95% CI 1.29 - 1.44), respectively. Conclusions: We found significant hospital and operator-level variation not only in post-PCI CR referral, but also CR utilization. Multi-faceted interventions targeting hospitals and PCI operators are needed to improve CR use after PCI.
Abstract 216: Tat Delivery of a Pten Peptide Inhibitor Has Direct Cardioprotective Effects and Improves Outcomes in Rodent Models of Cardiac Arrest
Authors: Xiangdong Zhu, Jing Li, Huashan Wang, Filip Gasior, Chunpei Lee, Shaoxia Lin, Zhiyi Zhu, J. Michael O'donnell, Terry L Vanden Hoek
Journal: Circulation (2020)

Introduction: We have recently shown that pharmacologic inhibition of PTEN significantly increases cardiac arrest survival in a mouse model, however, this protection required pretreatment 30 min prior to the arrest. To improve the onset of PTEN inhibition during cardiac arrest treatment, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) for rapid tissue delivery and protection. Hypothesis: We hypothesized that TAT-PTEN9c interferes with the endogenous PTEN binding to its regulatory proteins, resulting in reduced PTEN activity, improved mouse survival and cardiac functional recovery. The improved survival is in part due to enhanced glycolysis and reduced shunting to polyol pathway and osmotic injury in heart and brain. Methods: TAT-PTEN9c (7.5 mg/kg) was given intravenously after CA in mouse to determine protective effects of the treatment on survival and heart function. Western blot was used to determine the efficacy of TAT-PTEN9c for enhancing Akt and PDH E1α activity. The effect of TAT-PTEN9c on sorbitol accumulation in tissues was measured by spectrophotometer using NAD as substrate. Direct effect of TAT-PTEN9c treatment on cardiac function were also measured in Langendorff model of isolated rat heart. Results: In the mouse model of cardiac arrest, survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 4 h after CPR. The treated mice had increased Akt phosphorylation and pyruvate dehydrogenase dephosphorylation at R30 min in heart tissues with significantly decreased sorbitol content and reduced release of taurine and glutamate into blood, suggesting improved metabolic recovery and glucose utilization. For the isolated heart model, RPP was reduced by 25% for non-treatment groups following arrest. With TAT-PTEN9c treatment, cardiac contractile function was completely recovered. TAT-PTEN9c significantly increased lactate production at 20 min of reperfusion, indicating increased glycolysis. Conclusion: TAT-PTEN9c enhances Akt and pyruvate dehydrogenase activity and decrease glucose shunting to the polyol pathway in critical organs, preventing osmotic injury and early cardiovascular collapse and death.
Abstract 261: Acute Lung Injury and Recovery in Patients with Refractory Vf/vt Cardiac Arrest Treated with Prolonged Cpr and Veno Arterial Extracorporeal Membrane Oxygenation
Authors: Alejandra Gutierrez, Rajat Kalra, Demetris Yannopoulos, Jason Bartos
Journal: Circulation (2020)

Background: Post cardiac arrest syndrome includes significant pulmonary injury that is not clearly understood. Objectives: Describe the lung injury patterns among patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest (VT/VF OHCA) patients who were treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: OHCA characteristics, post-arrest computed tomography (CT) scans, ventilator parameters and complications were collected using a retrospective cohort design. Changes in lung compliance were compared over time between survivors, patients with acute brain death and those who had other modes of death with a two- way analysis of variance. Results: Among138 refractory VT/VF OHCA patients (81% were male with a median age of 59.0 years, mean CPR time of 64.3 ±16.1 min, a mean APACHE II score of 30.5 ± 4.6) 48/138 (34.8%) survived, acute brain death occurred in 48/138 (34.8%) and other modes of death in 56/138 (40.6%). The dependent posterior segments of the lung were the most commonly affected areas on the initial CT scan(Fig1A). There was no difference in the number of hyperattenuated areas between the survival groups.Compliance was borderline on day one (median 26.3(19.3,33.3)ml/cmH 2 0), but improved throughout the hospitalization (p=0.001) and was higher in survivors compared to those who died (p&lt;0.001, Fig1B). VA-ECMO allowed the use of lung-protective ventilation in patients with borderline compliances maintaining safe PaO2 and PaCO2. Patients additionally treated with IABP/Impella had lower pulmonary compliance and more hyperattenuated areas on their initial CT scan compared to those treated exclusively with VA-ECMO. Conclusions: Refractory VT/VF OHCA patients who are treated with VA-ECMO frequently have lung injury with borderline compliance soon after the index event. Lung compliance improves throughout hospitalization and is higher in survivors.