tbuckley/cabot-search huggingface dataset:
Abstract 13736: Elimination of Senescent Cells Targeting Senescence Associated Glycoprotein (sagp) Improved the Atherosclerosis and Diabetes
Authors: Masayoshi Suda, Ippei Shimizu, Goro Katsuumi, Yohko Yoshida, Yuka Hayashi, Tohru Minamino
Journal: Circulation (2020)

Cellular senescence entails an irreversible growth arrest and a pro-inflammatory secretory phenotype, which contributes to aging-associated disorders such as atherosclerosis and diabetes, however, underlying mechanisms are largely unknown. In this study, we identified a novel protein, senescence-associated glycoprotein (SAGP), as a biomarker of cellular senescence and we also found that elimination of senescent cells targeting SAGP attenuated aging-associated disorders such as atherosclerosis and diabetes. First, we identified that SAGP as a senescent marker by microarray analysis of senescent human endothelial cells compared with young endothelial cells. The expression of SAGP was significantly increased in the aorta of chronological aging mice or ApoE-knockout mice. Then we measured SAGP expression in the patients registered in our hospital and found that mean SAGP expression was significantly higher in patients with atherosclerotic diseases compared to patients without atherosclerotic diseases.Recently, it is reported that elimination of senescent cells (senolysis) reversibly improved pathological aging phenotypes and also extended the lifespan. We established senolytic therapy targeting SAGP. We generated SAGP-DTR (diphtheria toxin receptor) transgenic mice, in which we could eliminate the SAGP- positive senescent cells using DT (diphtheria toxin). We found elimination of SAGP positive senescent cells significantly reduced the atherosclerotic plaque burden in the aorta of ApoE-KO mice and improved the glucose metabolism of dietary obese mice. For clinical implication, we then developed a cytotoxic vaccine targeting SAGP. Treatment with SAGP vaccine successfully eliminated SAGP positive senescent cells and attenuated atherosclerosis and metabolic dysfunction. These data indicate that targeting SAGP-positive cells could be a novel strategy for senolytic therapy.
Abstract 15035: Managing Covid-19 Amongst Pediatric Heart Transplant Recipients in Sao Paulo, Brazil
Authors: Estela Azeka, Adam Arshad, Marcelo B Jatene
Journal: Circulation (2020)

Introduction: Heart transplant recipients are considered high risk for poor outcomes following Covid-19 infection. However, there is minimal literature on the effects of Covid-19 on this cohort. We provide our centres experience, as a developing nation with limited resources, in the prevention and management of Covid-19 amongst pediatric heart transplant recipients. Methods: 141 pediatric heart transplant recipients are currently followed-up at our centre - Heart Institute (InCor), Sao Paulo Medical School. We monitored this cohort using telephone contact, by which we postponed appointments and gave recommendations to stay home and maintain hygiene. Since March 2020, for any potential organ donations, a screening was conducted of the donor by taking a history, a RT-PCR-Covid 19 swab and performing a chest CT scan. Results: Five pediatric heart transplant recipients were suspected to have Covid-19 disease and two were tested positive for Covid-19. The first patient was a 14-year-old girl who underwent heart re-transplantation for coronary artery vasculopathy on March 5th, 2020. She developed significant haemodynamic compromise on post-operative day 45 and was transferred to ICU. Her chest CT showed extensive lung opacities (Figure 1). While attempting to wean her from mechanical ventilation, she had a sudden death. The second patient was a 6-year-old male. He presented to the hospital with vomiting, pyrexia, abdominal pain and nasal congestion. His chest CT scan demonstrated small nodule opacification of the lungs. He was appropriately commenced on fluids, antibiotics and antiviral medications. With improvements in his clinical state, he was discharged after 8-days. Conclusions: We provided telehealth to reduce the spread of Covid-19 amongst our cohort. However, we still had two Covid-19 positive cases at our centre. Our observations suggest that pediatric heart transplant recipients are at risk of deleterious outcomes from COVID-19 infection.
Differential Inhibition of E-S Potentiation and Long-term Potentiation by Cell-Derived and Arctic Amyloid Beta
Authors: Adrienne L Orr, Jason K Clark, Daniel V Madison
Journal: Alzheimers Disease & Dementia (2020)

Soluble oligomers of amyloid-beta peptide (Abeta) have been implicated in the onset of memory deficits in Alzheimer's disease, perhaps due to their reported ability to impair long-term potentiation (LTP) of synaptic strength. We previously showed the effect of Abeta on LTP depends on the strength of LTP induction. Furthermore, Abeta affects EPSP-Spike (E-S) potentiation more robustly than LTP, suggesting that E-S potentiation may be equally important to learning and memory in the context of Alzheimer's disease. Here we extend our findings to two additional forms of Abeta that form higher concentrations of soluble Abeta oligomers and show that they also affect E-S potentiation at induction strengths where there is no effect on LTP in hippocampal slices.
Abstract 14317: Kidney Function Deterioration is Dependent on Blood Pressure Levels: 11.2-year Follow-up in Diabetic Patients
Authors: Hirofumi SOEJIMA, Takeshi Morimoto, Sadanori Okada, Chisa Matsumoto, Masafumi Nakayama, Hideaki Jinnouchi, Izuru Masuda, Masako Waki, Yoshihiko Saito, Hisao Ogawa
Journal: Circulation (2020)

Introduction: Blood pressure (BP) is a significant predictor for chronic kidney disease (CKD). Hypothesis: We sought to evaluate whether the progression of CKD in diabetic patients, without a history of atherosclerotic events, is dependent on BP control. Methods: The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. We defined late-stage kidney disease (LSKD) as estimated glomerular filtration rate (eGFR) &lt;30 ml/min/1.73m 2 or hemodialysis. Among 2,536 JPAD patients, 27 patients were excluded for eGFR &lt;30ml/min/1.73m 2 on registration. BP of the JPAD patients was recorded on average 8 times. Based on the mean value of systolic BP (SBP), we divided the patients into three groups: a High BP Group (n=607, SBP≥140 mm Hg); a Moderate BP Group (n=989, 140&gt;SBP≥130 mm Hg); or a Low BP Group (n=913, SBP&lt;130 mm Hg). We compared the incidence of LSKD among the three groups. Results: The mean eGFR (ml/min/1.73m 2 ) was 75.1 in the High BP Group, 72.6 in the Moderate BP Group, and 75.7 in the Low BP Group on registration. During a 11.2-year follow-up, the incidence of LSKD was significantly higher in the High BP and Moderate BP Groups than in the Low BP Group (P&lt;0.0018, Figure). Cox proportional hazards model analysis revealed that the High BP (HR, 1.57, P=0.049) and Moderate BP (HR, 1.52, P=0.037) were independent factors after adjustment for proteinuria≥±, age≥65 years, men, body mass index≥24 kg/m 2 , duration of diabetes ≥7.0 years, statin usage, aspirin usage, eGFR≥60 ml/min/1.73m 2 , and hemoglobin A1c ≥7.2 % (Figure). Conclusions: Our study demonstrated that SBP was independently associated with the progression to LSKD in diabetic patients, without a history of atherosclerotic events. SBP less than 130 mm Hg is recommended for diabetic patients to prevent progression to LSKD.
Abstract 146: Association of Epinephrine Prior to Defibrillation with Survival in Patients with In-hospital Cardiac Arrest
Authors: Erin Evans, Morgan B Swanson, Nicholas Mohr, Boulos Nassar, Paul S Chan, Saket Girotra
Journal: Circulation (2020)

Background: Prompt defibrillation is a first line treatment for in-hospital cardiac arrest (IHCA) due to a shockable rhythm, with epinephrine recommended only when defibrillation is ineffective. However, empirical data regarding epinephrine prior to first defibrillation for shockable IHCA and its association with survival are unavailable. Methods: Using 2000-2018 Get with the Guidelines Resuscitation data, we identified adults ( &gt; 18 years) with an index IHCA due to an initial shockable rhythm. We conducted a time-dependent propensity-matched analysis to evaluate the association of epinephrine prior to first defibrillation with survival to discharge and acute resuscitation survival (i.e., return of spontaneous circulation for &gt; 20 minutes). Results: Among 34,688 subjects, 10,057 (29.0%) received epinephrine before defibrillation. Median age was 67 years in both groups. Compared to defibrillation first, patients in the epinephrine first group were less likely to have myocardial infarction or heart failure, but more likely to have renal failure, sepsis and pneumonia, be located in an intensive care unit, and already receiving mechanical ventilation (P &lt;0.001 for all). Treatment with epinephrine first was strongly associated with a delay in first defibrillation (median 3 min vs. 0 min; P &lt;0.001). In propensity-matched analysis, epinephrine prior to defibrillation was associated with lower odds of survival to discharge (OR: 0.81, 95% CI 0.76 - 0.86) and acute resuscitation survival (OR: 0.79, 95% CI 0.74 - 0.84). Early epinephrine was associated with lower survival (OR: 0.87, 95% CI 0.78-0.97) and acute resuscitation survival (OR for acute resuscitation survival: 0.83, 95% CI 0.74-0.93) even in patients who received defibrillation within 2 minutes. Conclusions: Despite a strong emphasis on prompt defibrillation in current guidelines, nearly 1 in 3 patients with IHCA due to a shockable rhythm received epinephrine prior to first defibrillation. Epinephrine before defibrillation was associated with worse survival outcomes. Although delays in defibrillation were more common in the early epinephrine group, early epinephrine remained associated with worse outcomes even in patients who received prompt defibrillation.
The Complicated Legacy of Cassandra Callender
Authors: Jonathan M. Marron, Elaine C. Meyer, Kerri O. Kennedy
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Feature-driven local cell graph (FLocK): New computational pathology-based descriptors for prognosis of lung cancer and HPV status of oropharyngeal cancers
Authors: Cheng Lu, Can Koyuncu, German Corredor, Prateek Prasanna, Patrick Leo, XiangXue Wang, Andrew Janowczyk, Kaustav Bera, James Lewis Jr., Vamsidhar Velcheti, Anant Madabhushi
Journal: Medical Image Analysis (2020)
Civil servants should be congratulated for rejecting "whole population theory"
Authors: J. Le Fanu
Journal: BMJ (1996)

EDITOR,-The report of the Interdepartmental Working Group on sensible drinking' has aroused critical comment.2The core recommendation is an increase in the safe limits for drinking from 21 units a week to 3-4 units a day for men and from 14 units a week to 2-3 units a day for women.The apparent aims are to discourage binge drinking and to promote health through moderate daily consumption.3We investigated how drinkers had interpreted the new guidelines and what effect the guidelines would have on their drinking.Over the Christmas
MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates
Authors: Juliette Hordeaux, Elizabeth L. Buza, Brianne Jeffrey, Chunjuan Song, Tahsin Jahan, Yuan Yuan, Yanqing Zhu, Peter Bell, Mingyao Li, Jessica A. Chichester, Roberto Calcedo, James M. Wilson
Journal: Science Translational Medicine (2020)

Inhibiting transgene expression with a tissue-specific microRNA target ameliorates AAV vector toxicity in NHPs.
Abstract 14498: MRI: Additive Value for the PM/ICD Device Patient; A Safety and Efficacy Study
Authors: Robert W Biederman, Loretta Gevenosky, Huma Samar, RONALD WILLIAMS, Richard Lombardi, Moneal Shah, Francesco Mangini, Victor Farah, Christopher Bonnet, Mark Doyle
Journal: Circulation (2020)

Introduction: While many studies have unequivocally demonstrated MRI safety in pts with thoracic devices, the clinical value is rarely considered. Yet, recent CMS-NCD supports more widespread considerations providing a unique opportunity for improved care. Hypothesis: We propose that MRI in pts with PM/ICDs are crucial to existing diagnosis and often substantially alters diagnosis and subsequent care. Methods: An evaluation of 1145 PM/ICDs pts who underwent MRI (GE 1.5T,WI) over 12 yrs (95% &lt;5yrs) was performed. The devices consisted of 665 PMs, 418 ICDs, 30 retained leads and 18 Loop/Linqs (some pts &gt;1). Specific criteria were followed to objectively determine if MRI diagnosis altered pt care. Accordingly, 4 Boolean Logic Construct questions were posed within 1 week of MRI by technologist/MD: 1) Did primary diagnosis change? 2) Did MRI provide additional diagnoses? 3) Was pre-MRI (tentative) diagnosis confirmed? 4) Did pt care change? If 'Yes' was answered to any question, MRI was considered of value to pt diagnosis and/or impending therapy. Result: Avg MRI: 34±21min. In 1145 pts: 819 (72%) were neuro/neurosurgery (NS), 110 (10%) were musculoskeletal (MK) and 216 (19%) were cardiac (CV) pts. On review, NS-MRI's, 669 (87%) provided additional information. The diagnoses changed in 553 (73%) and medical therapy changed in 536 (70%). In only 73(10%) did MRI simply confirm original diagnosis. In 216 CV cases, MRI provided additional data. In 178 pts (82%), MRI changed the original diagnosis and in 138 (64%), pt care. MRI was uninterpretable in 29 (11%; ICD artifact) while in 41 (19%) pts there was no diagnostic change. In essence, 174 (81%) of the CV cases benefited by MRI. Finally, in 110 MK cases, MRI provided additional data in 103 (96%), in 95 (88%) changed pt care and in 1 pt simply confirmed the diagnosis. Importantly, with careful attention to device reprogramming and scanner sequences, no safety/device issues occured. Conclusion: In 1145 pts with devices, MRI adds substantial clinical value to diagnosis and subsequent management justifying any residual risk. We believe, this is the largest study to focus solely on diagnostic value and efficacy under the assumption that safety can be routinely accomplished; a new paradigm in the error of a generation of non-CIED devices.
Abstract 17167: Black Women Have Evidence of Cardiometabolic Risk and Damage to the Microvascular Glycocalyx 1 to 10 Years After Uncomplicated Pregnancy
Authors: Robin Gandley, Robin Gandley, Marie Tuft, Arundhathi Jeyabalan, Mark K Santillan, Gary L Pierce, Gong Tang, Carl A Hubel, Janet M Catov
Journal: Circulation (2020)

Introduction: Endothelial glycocalyx (GCX) is a proteoglycan/glycoprotein rich surface layer that regulates vascular health and function and can be damaged in diabetes and cardiovascular disease. Given the excess risk of adverse pregnancy outcomes (APO), chronic hypertension and CVD in Black compared to White women, we considered that microvasculature and glycocalyx may also differ between groups and contribute to adverse clinical outcomes. Objective: The first step was examining the microvasculature in women with no complications in the index pregnancy (from the medical record) and cardiometabolic risk markers. Methods: Sidestream dark-field imaging of the sublingual microcirculation and glycocalyx was used to compare density, median diameter, perfusion (RBC filling %), and penetration of red cells into the glycocalyx of vessel segments of 20-25μm diameter (PBR), in women 1-10 years after the index pregnancy (mean 8 years after index pregnancy). The study included 67 Black women and 167 White women with no complications (preeclampsia, gestation hypertension, preterm delivery, intrauterine growth restriction or gestational diabetes) in the index pregnancy. Health and pregnancy history were obtained by questionnaire at the study visit. Results: Black women had a greater penetration of red blood cells into the glycocalyx of microvascular segments20-25μm (PBR:2.54±0.41 vs White women 2.40±0.43μm, p=0.02). Perfusion in Black women was reduced (70.5±4.2% vs 72±4.8% p=0.003) compared to white women. Associations remain after adjusting for age, BMI, and time to follow-up. Black women were significantly younger (25± 6 vs 30±5 yrs p&lt;0.001) at index delivery and study visit (34±6 vs 38±6yrs p=0.001); they also had higher BMI both pre-pregnancy (28±7 vs 25±6, p=0.007) and at the study visit (32±7 vs 27±7, p&lt;0.001) and higher fasting insulin(17±36 vs 7±9 p=0.002) at the visit compared to White women. Self-reported history of hypertension, diabetes and APO (outside the index pregnancy) was significantly more common among Black at follow-up. Conclusion: Compared to White women, Black women of reproductive age had evidence of more pronounced microvascular changes potentially related to cardiometabolic risk 1-10 years after an uncomplicated index pregnancy.
Abstract 15848: Impact of the Covid-19 Pandemic on D2B Activations in a Single, Tertiary Care, Urban Medical Center in the United States
Authors: Philip Lavenburg, Michael Gannon, Brian O'Murchu, Vladimir Lakhter, Deborah L Crabbe, Riyaz Bashir
Journal: Circulation (2020)

Introduction: Initial reports suggest that patients may delay seeking medical attention during the Coronavirus Disease 2019 (COVID-19) pandemic. Our aim was to determine if the COVID-19 outbreak is associated with a higher incidence of late presentations for patients with STEMI, greater need for mechanical circulatory support and PCI. Methods: We retrospectively evaluated consecutive patients that presented to a single, academic medical center with acute chest pain and ST-segment elevation on ECG from March 15 through June 17 in years 2019 and 2020. All patients were referred for emergent coronary angiography and the final cohort consisted of 32 patients. Medical records were reviewed to determine time between symptom onset and hospital arrival, need for PCI and/or mechanical circulatory support, total fluoroscopy time and volume of contrast administration during catheterization. Results: There was no significant difference in age, gender, cardiac risk factors or history of CAD between the cohorts that presented in 2019 compared with 2020 (Table 1). The mean time from symptom onset to arrival in the ED was 6.5 ± 8 and 9.2 ± 17 hours in 2019 and 2020 (p=0.55), respectively. PCI was performed during the index catheterization in 5 (50%) and 21 (95%) patients in 2019 and 2020 (p=0.01), respectively. Mean volume of contrast media used per case was 142 ± 65 ml in 2019 and 237 ± 104 ml in 2020 (p=0.017). There was a trend towards greater need for mechanical circulatory support and total fluoroscopy time during cases in 2020 (Table 1). Conclusions: In patients with suspected STEMI during the COVID-19 pandemic, there was a trend towards longer duration between symptom onset and arrival to the ED. More patients presenting with ST-segment elevation required PCI and there was a trend towards greater utilization of mechanical circulatory support. These findings may reflect a decline in access to outpatient services and/or delays in patients seeking care for acute chest pain.
Abstract 309: Prediction Chart for Neurological Outcomes of Elderly Patients with Out-of-hospital Cardiac Arrest and the Corresponding Time to Termination of Resuscitation: Evidence from a Japanese Nationwide Population-based Cohort Study
Authors: Akira Funada, Yoshikazu Goto, Masayuki Takamura
Journal: Circulation (2020)

Introduction: Neurological outcomes and the appropriate duration from call receipt to termination of resuscitation (TOR) in patients with out-of-hospital cardiac arrest (OHCA) could differ according to patient characteristics. Hypothesis: We hypothesized that a prediction chart comprising prehospital variables, including age, could be useful for predicting neurological outcomes and determining the time to TOR in the field or at the emergency department. Methods: We evaluated 19,829 elderly patients with OHCA (age ≥65 years) of cardiac origin who achieved prehospital return of spontaneous circulation (ROSC). Data were obtained from the prospectively recorded All-Japan Utstein Registry between 2011 and 2016. Patients with OHCA witnessed by emergency medical service providers were excluded. The primary outcome was 1-month neurologically intact survival, defined as a cerebral performance category (CPC) score of 1-2. Patients with OHCA were divided into 12 groups according to shockable rhythm (YES/NO), witness status (YES/NO), and age (65-74, 75-89, or ≥90 years). The time from call receipt to ROSC was calculated and categorized by 5-min intervals. The time from call receipt to ROSC at which the probability of 1-month CPC 1-2 decreased to &lt;1% was defined as the call to TOR duration. Results: The overall 1-month CPC 1-2 rate was 18.9% (n = 3,756). When stratified by patient characteristics, the 1-month CPC 1-2 rates ranged from 52.3% in patients aged 65-74 years with shockable rhythm and witnessed OHCA (best-case scenario) to 1.6% in patients aged ≥90 years with non-shockable rhythm and un-witnessed OHCA (worst-case scenario). The corresponding call to TOR duration ranged from 35 to 10 min (Table). Conclusions: Neurological outcomes and the appropriate call to TOR duration differed according to patient characteristics, including age. Our prediction chart for elderly patients with OHCA could be useful for determining TOR in the field or at the emergency department.