tbuckley/cabot-search huggingface dataset:
Abstract 17804: Prediabetes and Stroke Risk in Hospitalized Non-Diabetic Geriatric Patients With Atrial Fibrillation: Unfurling the Association Through Population-Based Analysis
Authors: Shrikanth Sampath, Archit Srivastava, Pooja Suchday, Aditi K Bhanushali, Alkananda Behera, KAMYA MEHTA, Akhil kumar Eppalapally, Ram Prasanjith Reddy Bollampalli, Rupak Desai
Journal: Circulation (2023)

Background: The association of prediabetes (pDM) with stroke risk in non-diabetic geriatric patients with AF is unclear. The findings from this analysis contribute to a better understanding of the interrelation between pDM, AF, and stroke, highlighting the need for targeted interventions and risk management strategies in this vulnerable population. Methods: Utilizing the 2019 National Inpatient Sample and employing ICD-10 CM coding, we identified all non-diabetic geriatric admissions with AF. Patients were categorized into two groups: pDM+ and pDM-. The primary outcomes of interest were stroke incidence, odds and potential sex disparities in odds as a risk factor for stroke in geriatric patients with AF. Results: Of the total 218130 non-diabetic geriatric AF admissions, 3525(1.6%) had pDM. The pDM+ cohort was relatively younger (median 75 vs 77 years), and often consisted of females (57.9%; p&lt;0.359), white (80.1%), and from the higher-income quartile (28.5%); (p&lt;0.001). The preDM+ group had significantly higher rates of complicated HTN (50.2 vs 43.6%), hyperlipidemia (66.4 vs 53.7%), obesity (30.2 vs 13.6%), PVD (15.3 vs 9.9%), stroke (1.4 vs 0.8%). After adjusting for baseline characteristics/comorbidities, the pDM+ cohort with AF admissions showed a higher rate and significantly higher odds of stroke vs the pDM- cohort (1.4% vs. 0.8%, OR 2.00, 95%CI 1.06-3.77; p=0.033). On subgroup analyses, males had a stronger association (OR 5.48, 95%CI 1.43-21.02; p=0.013) vs. females. Conclusion: Our research revealed that geriatric patients hospitalized with AF who had concomitant pDM were twice likely to develop stroke, with male preponderance. Further research is warranted to develop tailored interventions to mitigate the risk of stroke in AF patients with pDM.
Abstract 17622: CCN3 Deficiency in Myeloid Cells Exacerbates Aortic Dissection by Governing a Proinflammatory Program in Macrophages
Authors: Qian Xu, Xianming Zhou, Hildebrando C Ferreira Neto, Zhiyong Lin
Journal: Circulation (2023)

Introduction: Aortic dissection (AD) is a fatal disease. Macrophages are known central regulators of aortic inflammation and elastic fiber disruption, two major hallmarks of AD. Cellular communication network factor 3 (CCN3/NOV) is a matricellular protein associated with various biological cellular functions in cardiovascular disease and cancers. Emerging evidence strongly implicates a protective role of CCN3 against several types of vascular pathologies, however its role in AD remains unknown. Hypothesis: CCN3 deficiency in myeloid cells promotes AD development in murine models through the modulation of macrophage phenotype. Aims: We investigated the causal role of CCN3 loss in AD pathogenesis, focusing on its role in macrophages. Methods: 3-4-week-old male myeloid-specific CCN3 knockout mice (CCN3F/F;LysMCre) and control mice (LysMCre) were given BAPN (β-aminopropionitrile monofumarate; 0.2%) in their drinking water for 4 weeks for AD modeling. Mouse survival rate and histological changes of the aorta were assessed. Single cell RNA sequencing analysis was performed to recapitulate cellular transcriptome profile changes. Finally, gain and loss of function studies in bone marrow-derived macrophages (BMDMs) were performed to decipher the underlying mechanism by which CCN3 controls macrophage plasticity. Results: Following BAPN administration, myeloid-specific CCN3 knockout mice had a higher mortality rate due to AD formation and aortic rupture. In accordance with this phenotype, vascular media thickness was markedly reduced, and elastic fiber fragmentation and macrophage infiltration were elevated in myeloid-specific CCN3 knockout mice. Using single-cell RNA-seq, we found that myeloid-deficiency of CCN3 was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages. Furthermore, CCN3 deficient BMDMs are prone to M1 macrophage polarization, an effect dependent on the activation of the JAK/STAT1 signaling pathway. Conclusions: Myeloid-deficiency of CCN3 drives vascular macrophages toward an M1-like, pathogenic phenotype and promotes dissecting aortic aneurysm.
Abstract 273: Development and Implementation of a Multicenter Registry for Resuscitation-Focused Transesophageal Echocardiography
Authors: Felipe Teran, Clark G Owyang, Trenton Wray, John Hipskind, Justine Lessard, William Bédard Michel, Chantal Lanthier, Peiman Nazerian, Eleonora de Villa, Jonathan Nogueira, Daniel Doynow, Michelle Clinton, Frank Myslik, Ross Prager, Robert Arntfield, Pedro D Salinas, Vladyslav Dieiev, Michael Y Woo, Rajiv Thavanathan, Graeme Puskas, Karan Singh, Priyanka Bhat, Jackson Horn, Brian M Buchanan, Nadia Baig, Katharine Burns, Kelsey Kennedy, Lawrence Haines, Leily Naraghi, Harpriya Singh, Michael Secko, Daniel Singer, Maria Taylor, John M Joyce, Stephanie DeMasi, Zan M Jafry, Tammy Phan, Natalie Truong, Evan Robinson, Korbin H Haycock, Allyson Hansen, Charlotte Derr, Phillip Andrus, Junaid Razzak, Joanna Palasz, Aarthi Kaviyarasu, Nathaniel A Sands, Benjamin S Abella
Journal: Circulation (2023)

Objectives: To evaluate the clinical impact, safety, and clinical outcomes of focused transesophageal echocardiography (TEE) in the evaluation of critically ill patients in the emergency department (ED) and intensive care units (ICU). Methods: We established a prospective, multicenter, observational registry involving adult critically ill patients in whom focused TEE was performed for evaluation of out-of-hospital cardiac arrest (OHCA), in-hospital cardiac arrest (IHCA), evaluation of undifferentiated shock, hemodynamic monitoring, and/or procedural guidance in the ED, ICU, or operating room (OR) setting. The primary objective of the current investigation was to evaluate the clinical impact and safety of focused, point-of-care TEE in critically ill patients. Data elements included patient and procedure characteristics, laboratory values, timing of interventions, clinical outcomes, and TEE video images. Results: A total of 771 cases were collected from 27 hospitals, including 506 (66%) intra and post arrest OHCA and IHCA, 221 (29%) initial evaluation of undifferentiated shock, 71 (9%) hemodynamic monitoring, and 93 (12%) procedural guidance. TEE changed management in 64% of cases of OHCA, in 71% of IHCA, and in 85% of patients with undifferentiated shock. There were no reported esophageal perforations or oropharyngeal injuries, and other procedural complications were rare. Conclusion: A prospective, multicenter, and multidisciplinary TEE registry was successfully implemented, and demonstrated that focused TEE is safe and clinically impactful across multiple critical care applications. Further studies from this research network will accelerate the development of outcome-oriented research and knowledge translation on the use of TEE in emergency and critical care settings.
Abstract 16011: Lymphatic Intervention Following Superior Cavo-Pulmonary Anastomosis Potentially Allows for Successful Fontan Completion
Authors: Danish Vaiyani, Brooke Ford, Mudit Gupta, Thomas Dietzman, David Biko, Aaron G DeWitt, Matthew Gillespie, Michael L Obyrne, Jonathan Rome, Christopher Smith, Yoav Dori
Journal: Circulation (2023)

Introduction: Superior cavopulmonary anastomosis (SCPC) inevitably exposes the thoracic duct to higher venous pressure, potentially triggering disordered lymphatic perfusion manifesting as chylothorax (CT) and/or plastic bronchitis (PB) . Though outcomes following lymphatic interventions after Fontan completion (FC) are well described, they are not well described in patients after SCPC. Methods: A single-center retrospective study of patients who underwent lymphatic intervention for PB or CT following SCPC 1/1/2011-12/31/2021 was performed, excluding those with planned two ventricle or 1.5 ventricle repair, patients who underwent thoracic duct ligation, and those in whom interventions were performed either prior to SCPC or following FC. Results: In total, 27 patients (56% male) were studied, of which 22% had PB and 78% with CT, 7% with Noonan’s syndrome and 19% with heterotaxy syndrome. Median age at intervention was 11.3 months (IQR 7.4 - 33.5). Median time following SCPC was 3.5 months (IQR 2.1 - 24.2). In terms of interventions, 41% (n=11) underwent selective lymphatic channel embolization. Of these 36% (4/11) underwent subsequent thoracic duct embolization (TDE). The remaining 59% (n=16) patients underwent TDE. The thoracic duct was able to be accessed in 23 patients (85.2%). Twenty-four patients (19/21 with CT, 5/6 with PB) had resolution of symptoms following transcatheter intervention at our center. Following intervention, seven patients (all of whom were of the type IV lymphatic subtype) were successfully referred for FC, ten are currently awaiting FC, five are not Fontan candidates and five passed away from non-procedural comorbidities. Median duration of post-operative chest tubes following FC was 7 days (IQR 6-8) and median follow up is 39.1 months (IQR 15.1 - 45.1). Conclusions: Selective lymphatic embolization and TDE are feasible in SCPC recipients with CT and PB, with most patients experiencing symptomatic improvement. Subsequent FC has been achieved in some patients with type IV lymphatic abnormalities, suggesting that these interventions may alter the unnatural history of lymphatic dysfunction in single ventricle patients. Future research is needed to define longer term outcomes of this high-risk cohort.
Abstract 141: Automated Head-Up Cardiopulmonary Resuscitation Increased End Tidal Co2 in Patients With Out-of-Hospital Cardiac Arrest Compared With Conventional CPR: A Prospective Before-After Interventional Study
Authors: Guillaume Debaty, Helene Duhem, Nicolas Segond, caroline sanchez, Christophe Crespi, Deborah Jaeger, Tahar Chouihed, Keith G Lurie, José Labarere
Journal: Circulation (2023)

Background: Little is known in humans about the physiological effects of the combination of automated Head-Up cardiopulmonary resuscitation CPR, active compression-decompression CPR and an impedance threshold device (ITD). This new approach, termed AHUP-CPR, improves perfusion of vital organs and lowers intracranial pressure compared with conventional (C)CPR in animal models of cardiac arrest. This study tested the hypothesis that AHUP-CPR treatment would increase end tidal CO2 (ETCO2), a circulation surrogate, more than C-CPR in out-of-hospital cardiac arrest (OHCA) patients. Method: Prospective before-after interventional study of witnessed OHCA patients. C-CPR and AHUP-CPR were performed by firefighters who measured ETCO2. AHUP-CPR was delivered using a LUCAS AD (5 cm of compression and 3 cm active decompression) (Stryker Medical, USA), an EleGARD Patient Positioning System (AdvancedCPR Solutions, USA), and an ITD (ResQPOD-16, Zoll, USA). The study was performed in the greater Grenoble France region in four different fire stations. The primary endpoint was the measurement of maximum EtCO2 during CPR. Results are presented as mean ± standard deviation. Results: Baseline characteristics (age, sex, arrest location, initial rhythm, bystander CPR, witnessed) were not statistically different between groups.EtCO2 was higher for patients treated with AHUP-CPR (n=63) compared to the C-CPR (n=59) (41±18 vs. 30.2 mmHg, p&lt;0.001). This difference was significant for shockable (45±13 vs. 34±12 mmHg, p=0.03) and non-shockable (40±19 vs. 28±13 mmHg, p=0.004) rhythms, respectively. The calculated difference between the maximum and first recorded ETCO2 values was 6.3 ± 20.4 in the C-CPR arm versus 21.1 ± 20.6 in the AHUP-CPR group (P&lt;0.001). A total of 29% (n=18) of the AHUP patients vs. 22 % (n=13) were admitted alive to the hospital (P=0.34). Conclusion: Results from this first prospective clinical trial on AHUP-CPR demonstrated that ETCO2 values were significantly higher after AHUP-CPR versus C-CPR, regardless of the presenting rhythm. Using ETCO2 as a surrogate for circulation, these findings confirm animal studies showing AHUP-CPR provides significantly more vital organ blood flow to patients in OHCA compared with C-CPR.
Abstract 17565: Sympathetic Neural Overactivity, Endothelial Dysfunction, Aortic Stiffening, and Diminished Exercise Capacity in Breast Cancer Survivors Treated With Doxorubicin and Trastuzumab-Based Chemotherapy
Authors: Joao Izaias, Renata Bernardes, Bruna Ono, Diego Faria, Artur Sales, Laura Testa, Camila Moniz, Mauricio Mota, Vera M Salemi, Matthew Rossman, Daniel Craighead, Zachary Clayton, Luiz Bortolotto, Maria C Irigoyen, Fernanda Colombo, Douglas Seals, Allan Kluser
Journal: Circulation (2023)

Introduction: Previous evidence demonstrates that breast cancer (BC) survivors who were treated with doxorubicin and trastuzumab-based chemotherapy have an increased risk of developing cardiovascular (CV) disease at least 7 years after completion of cancer treatment. The reasons for the increased CV disease risk are not completely understood, a constellation of physiological changes may contribute. We hypothesized that BC survivors compared with age- and body mass index (BMI), sex -matched healthy controls, exhibit sympathetic neural overactivity, vascular endothelial dysfunction, aortic stiffening, and diminished exercise capacity. Methods: Twelve women BC survivors, treated with doxorubicin and trastuzumab (age=48±2 years and BMI=28±2 Kg/m 2 ) and fourteen women control subjects (age=46±1 years and BMI=27±1 Kg/m 2 ) were studied. Muscle sympathetic nerve activity (MSNA, Microneurography), endothelium-dependent dilation (brachial artery flow-mediated dilation, BAFMD), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), blood pressure (BP, Finometer), heart rate (HR, Electrocardiogram), and peak oxygen uptake (V˙O 2 peak, Cardiopulmonary exercise testing) were measured. Results: BC survivors were evaluated 8±2 years after the completion of cancer treatment. Burst frequency and burst incidence of MSNA were higher and BAFMD and V˙O 2 peak were lower in BC survivors than in controls ( p &lt;0.001). There were not differences between the groups in CFPWV, BP, and HR ( p &gt;0.05). MSNA burst frequency and burst incidence were inversely associated with V˙O 2 peak or BAFMD ( p &lt;0.05). Conclusion: Our findings demonstrate that BC survivors have an augmented sympathetic neural activity, endothelial dysfunction, and attenuated exercise capacity, which may help to explain, at least in part, the increased CV risk in this population. Therefore, it is urgent to establish therapeutic strategies (e.g., physical exercise rehabilitation) to restore or alleviate these cardiovascular changes in BC survivors.
Microglial APOE4: more is less and less is more
Authors: Ghazaleh Eskandari-Sedighi, Mathew Blurton-Jones
Journal: Molecular Neurodegeneration (2023)

Abstract Apolipoprotein E (APOE) is the single greatest genetic risk factor for late onset Alzheimer’s disease (AD). Yet, the cell-specific effects of APOE on microglia function have remained unclear. Fortunately, two comprehensive new studies published in the latest issue of Nature Immunolog y have employed complementary gain-of-function and loss-of-function approaches to provide critical new insight into the impact of microglial APOE on AD pathogenesis.
Abstract 17631: Diabetic Retinopathy and Risk of Heart Failure Subtypes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Justin B Echouffo, Chiadi E Ndumele, Sui Zhang, A R Sharrett, Kuni Matsushita, Josef Coresh, Amil M Shah, Elizabeth Selvin
Journal: Circulation (2023)

Introduction: Although diabetic retinopathy is associated with higher risk of incident heart failure (HF), its associations with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]) largely remain unknown. Hypothesis: Diabetic retinopathy, a microvascular complication of hyperglycemic states, is more strongly associated with HFpEF than with HFrEF. Methods: We included 5038 ARIC participants who underwent fundus photography at Visit 3 (1993-1995), had diabetes or prediabetes, and were free of HF (mean age 60 years, 48% women, 27% Black adults). Retinopathy was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) grading scale, with a severity score ≥14 defining the presence of any retinopathy. We used data on incident HF hospitalization. Information on HF subtypes was only available from 2005 onwards. We used Cox regression to estimate the associations of retinopathy with incident overall HF. For HF subtypes, to account for the competing risks of HFpEF and HFrEF, we used competing risks regression analysis by the proportional sub-hazards Fine and Gray method. Results: Over a median 21.2 years of follow-up, there were 1358 HF events (461 prior to 2005 and 897 post-2005 [including 418 HFpEF and 383 HFrEF]). The presence of diabetic retinopathy conferred higher risk of overall HF (hazard ratio [HR]: 1.84, 95% confidence interval [CI]: 1.55, 2.20). Among participants with information on HF subtypes post-2005 (n= 4120), diabetic retinopathy significantly increased the risk of HFpEF (HR 1.86, 95% CI: 1.28, 2.71), but not of HFrEF (sub-HR: 0.73, 95% CI: 0.45, 1.20). An increasing severity of diabetes retinopathy was associated with increasing risks of overall HF and HFpEF. Conclusions: The presence of diabetic retinopathy signifies an excess risk of HF, primarily HFpEF. Our findings support a strong contribution of microvascular disease to the development of HFpEF.
Thyroid Dermopathy in Graves’ Disease
Authors: Durairaj Arjunan, Sanjay K Bhadada
Journal: New England Journal of Medicine (2023)

A 49-year-old woman with Graves’ disease presented with a 3-year history of skin changes on her arms and legs. There were violaceous, nonpitting, indurated nodules on the dorsa of her hands, distal forearms, and shins.
Changing the Orbit around Percutaneous Coronary Intervention for Stable Angina
Authors: Harvey D. White
Journal: New England Journal of Medicine (2023)

The primary aim of treating patients with stable angina is to decrease symptoms and improve quality of life. Percutaneous coronary intervention (PCI), a treatment for patients with angina, does not reduce the risk of death from any cause, death from cardiac causes, or myocardial infarction.1 In this issue of the Journal, Rajkumar and colleagues2 report on the results of the ORBITA-2 trial, which is the first double-blind, randomized, placebo-controlled trial to show that PCI is an effective antianginal treatment in patients with stable angina who have objective evidence of ischemia. ORBITA-2 was an elegant and rigorous trial that was designed . . .
Emerging threats: global distribution and diversity of carbapenem resistance genes in Kluyvera intermedia
Authors: Daniel F M Monte, Mateus Lacerda Pereira Lemos, Celso José Bruno de Oliveira
Journal: The Lancet Microbe (2023)

Kluyvera intermedia, a ubiquitous species of enterobacteria, which has the potential to harbour and spread antimicrobial resistance genes associated with critically important antimicrobials in human medicine, has been underestimated. The fight against antimicrobial resistance (AMR) depends on our ability to identify the drivers of AMR dissemination. Therefore, researchers need to develop a more holistic understanding of the epidemiology of AMR.1 Although extensive information of AMR mechanisms in pathogens isolated from clinical cases has been accumulated, which is the tip of the iceberg, little is known about less-studied organisms such as K intermedia that might play an important role as reservoirs and spreaders of AMR.
Doxycycline Postexposure Prophylaxis for STIs in Women — Uncertain Benefit, Urgent Need
Authors: Jeanne Marrazzo
Journal: New England Journal of Medicine (2023)

The global incidence of reportable sexually transmitted infections (STIs), including gonorrhea, chlamydia, and syphilis, remains high and in some populations has relentlessly increased. In the United States in 2021, the incidence of early syphilis among men who have sex with men surpassed any previous record.1 The human and economic consequences of untreated STIs can be severe. Moreover, concurrent acquisition of human immunodeficiency virus (HIV) infection and another STI continues to occur, especially with a lack of HIV preexposure prophylaxis (PrEP), and the presence of STI increases the risk of HIV acquisition in this context. What is fueling this increase, and . . .
Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women
Authors: Jenell Stewart, Kevin Oware, Deborah Donnell, Lauren R. Violette, Josephine Odoyo, Olusegun O. Soge, Caitlin W. Scoville, Victor Omollo, Felix O. Mogaka, Fredericka A. Sesay, R. Scott McClelland, Matthew Spinelli, Monica Gandhi, Elizabeth A. Bukusi, Jared M. Baeten
Journal: New England Journal of Medicine (2023)

Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. Download a PDF of the Research Summary. We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P=0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae–positive isolates were resistant to doxycycline. Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.) QUICK TAKE VIDEO SUMMARYDoxycycline Prophylaxis to Prevent STIs in Women 02:28