tbuckley/cabot-search huggingface dataset:
Evolution and Diversity of Immune Responses during Acute HIV Infection
Authors: Samuel W. Kazer, Bruce D. Walker, Alex K. Shalek
Journal: Immunity (2020)

Understanding the earliest immune responses following HIV infection is critical to inform future vaccines and therapeutics. Here, we review recent prospective human studies in at-risk populations that have provided insight into immune responses during acute infection, including additional relevant data from non-human primate (NHP) studies. We discuss the timing, nature, and function of the diverse immune responses induced, the onset of immune dysfunction, and the effects of early anti-retroviral therapy administration. Treatment at onset of viremia mitigates peripheral T and B cell dysfunction, limits seroconversion, and enhances cellular antiviral immunity despite persistence of infection in lymphoid tissues. We highlight pertinent areas for future investigation, and how application of high-throughput technologies, alongside targeted NHP studies, may elucidate immune response features to target in novel preventions and cures.
Abstract 16799: Left Ventricular Hypertrophy in South African Adults and Children
Authors: Andrea Kolkenbeck Ruh, Larske Soepnel, Shane Norris, Justine Davies, Sanushka Naidoo, Lisa Ware
Journal: Circulation (2020)

Introduction: Left ventricular hypertrophy (LVH) increases risk of heart failure and sudden cardiac death. Specific changes in LV geometry and relative wall thickness (RWT) may provide additional prognostic information. As routine echocardiography may not typically be available in low-resource settings, we aimed to identify the factors associated with LVH presence and LV remodelling within adults (n=108; age 29-68 years) and children (n=56; age 4-10) in an urban cohort from a historically disadvantaged township in South Africa. Methods: Anthropometry and blood pressure (BP) were measured in triplicate, and self-reported diabetes mellitus, previous heart disease and hypertension medication, tobacco and alcohol use were recorded. LV mass was assessed at end-diastole perpendicular to the long axis of the LV and indexed to body surface area (LVMI). Prevalence of LVH (defined as LVMI&gt;95g/m 2 for adults and LVMI &gt;88.9g/m 2 [95 th percentile] for children), eccentric LVH (LVH with RWT&lt;=0.42) and concentric LVH (LVH with RWT&gt;0.42) and concentric remodelling (normal LVMI with RWT&gt;0.42) was recorded. For adults, hypertension was defined as BP ≥140/90 mmHg or on medication and for children using American Academy of Paediatrics Guidelines (2019). Body mass index (BMI) was calculated as weight (kg)/height(m) 2 . Results: LVH prevalence was 35.2% in adults (n=38; 74% eccentric LVH; 26% concentric LVH), and 12.5% (n=7) in children, all of which were eccentric LVH. Prevalence of concentric remodelling was 16.7% (n=18) in adults and 3.6% (n=2) in children. Hypertension prevalence was 38.9% (n=42) for adults and 53.6% (n=30) for children. LVH was present in 15.4% of normotensive children and 40.9% of normotensive adults. Multivariate logistic regression with age, BMI, hypertension and diabetes status, previous heart disease, tobacco and alcohol use showed only current tobacco use (OR 10.60 [1.72-65.25] p=0.01) increased the odds of concentric LVH in adults. Conclusions: Approximately one third of adults and one in ten children had LVH, with eccentric LVH the predominant type of remodelling. Hypertension prevalence in this population was also high. This preliminary analysis supports public health efforts for tobacco cessation to impact overall cardiovascular risk.
Abstract 459: Oxidized CaMKII Causes Atrial Fibrillation Susceptibility in a Diabetic Mouse Model
Authors: Olurotimi O Mesubi, Adam G Rokita, Biyi Chen, Long-Sheng Song, Xander H Wehrens, Mark E Anderson
Journal: Circulation Research (2016)

Background: Atrial fibrillation (AF) and diabetes mellitus (DM) are major, unsolved public health problems. DM is a known risk factor for AF, and both are associated with increased reactive oxygen species (ROS), suggesting a ROS responsive disease signal could be a mechanistic link between them. The multifunctional Ca2+ and calmodulin-dependent protein kinase-II (CaMKII) is activated by oxidation of paired methionines. Oxidized CaMKII (ox-CaMKII) is increased in atria from DM patients and causes ryanodine receptor (RyR2) hyperphosphorylation that promotes pathological intracellular Ca2+ release and Ca2+ triggered arrhythmias. We hypothesize that DM increases myocardial ox-CaMKII, RyR2 hyperphosphorylation and AF. Methods and Results: C57BL/6J mice with streptozocin-induced type 1 DM had increased AF susceptibility following atrial burst pacing compared with citrate buffer-treated wild-type (WT) controls [70% (14/20) vs. 25% (5/20), p = 0.01]. Ox-CaMKII was increased in atrial tissue from diabetic mice compared to controls, consistent with a role for ox-CaMKII in this model. Diabetic ox-CaMKII resistant knock-in (MM-VV) mice (37.5% (9/24) [p &lt; 0.05]) and diabetic mice with myocardium-restricted transgenic overexpression of methionine sulfoxide reductase A (25% (5/20) [p &lt; 0.05]), which reverses ox-CaMKII, were protected from DM increased AF susceptibility compared to diabetic WT controls. Atrial myocytes from diabetic WT mice demonstrated increased RyR2 mediated Ca2+ spark frequency, triggered action potentials and delayed intracellular [Ca2+] decay compared to controls. Diabetic knock-in mice resistant to CaMKII-mediated RyR2 phosphorylation (S2814A) had decreased AF susceptibility (25% (5/20) [p &lt; 0.05]), compared with diabetic WT mice. All groups of diabetic mice had similar increases in plasma glucose. Conclusions: Hyperglycemia increases AF susceptibility and increased ox-CaMKII is associated with increased AF in this diabetic mouse model. Genetic manipulation of an ox-CaMKII pathway can protect against AF susceptibility in DM. These findings suggest that ox-CaMKII is a critical proarrhythmic signal in DM and a potential therapeutic target for AF management in DM patients.
HIV prevention injection is more effective than daily pill, trials show
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A long acting form of the drug cabotegravir, which is taken once every eight weeks, is safe and more effective than the current daily oral pre-exposure prophylaxis (PrEP) Truvada for preventing HIV in women, according to the US National Institutes of Health (NIH).

A phase III trial comparing the two treatments will now end early after interim analysis showed that while both were effective at preventing HIV, cabotegravir was 89% more effective.

This comes after a similar study testing the injection in men and transgender women was stopped in July after it found that incidence of HIV was 66% lower in the cabotegravir injection group …
Recent developments in controlling sternal wound infection after cardiac surgery and measures to enhance sternal healing
Authors: Aathira Pradeep, Jayakumar Rangasamy, Praveen Kerala Varma
Journal: Medicinal Research Reviews (2020)

Abstract One of the major risks of cardiac surgery is the occurrence of infection at the sternal wound site. Sternal wound infections are primarily classified into superficial infection and deep sternal wound infection or mediastinitis. A patient is diagnosed with mediastinitis if microorganisms are present in their mediastinal tissue/fluid or with the observation of sternal wound infection during operation and with characteristic symptoms including chest pain, fever, and purulent drainage from the mediastinum. It is usually caused by Staphylococcal organisms in 75.8% of cases and the rest is caused by gram‐negative bacteria. Currently, in cardiac surgery, hemostasis is achieved using electrocautery and bone wax, and the sternum is closed using wire cerclage. Several studies show that bone wax can act as a nidus for initiation of infection and the oozing blood and hematoma at the site can promote the growth of infectious organisms. Many research groups have developed different types of biomaterials and reported on the prevention of infection and healing of the sternum. These materials are reported to have both positive and negative effects. In this review, we highlight the current clinical practices undertaken to prevent infection and bleeding as well as research progress in this field and their outcomes in controlling bleeding, infection, and enhancing sternal healing.
Abstract 14978: Heart Failure Patient Adherence and Decreased Perception of Illness During Remote Hemodynamic Monitoring
Authors: Lisa D Rathman, Samuel F Sears, Robert C Capodilupo, Robert C Bourge, Akshay S Desai, J Thomas T Heywood, John Henderson, Philip Adamson, Marie-Elena Brett, Lynne W Stevenson
Journal: Circulation (2020)

Introduction: Effective management of ambulatory heart failure (HF) requires active patient (pt) participation. In telemonitoring of weights and symptoms, pt adherence to transmission is often halved within 6 months (M). Although ambulatory pulmonary pressure-guided management decreases hospitalizations and improves quality of life, the time course of pt perception of illness and sense of security in relation to monitoring frequency is not known. Hypothesis: Pts will perceive decreased impact of their HF during pulmonary pressure-guided management, which may contribute to their engagement in transmission of ambulatory PAP. Methods: The post-approval study for the implanted PA sensor was amended to include serial measurements of pt reported outcomes, (PRO, n=143), including the Brief Illness Perception Questionnaire (BIPQ). Treatment was adjusted to a target PA diastolic pressure 8 to 20 mmHg and adherence to transmitting pressure data from home was collected. Results: In the PRO cohort, mean age was 68 years, 58% were male, and 55% with HFpEF. Negative illness perception (BIPQ) decreased during each measurement interval. Pts reported improvement in symptoms, sense of security, sense of control and less impact of illness on their emotions at each time point, equally with HFpEF or HFrEF. In this cohort pt adherence to transmitting pressures was high throughout 24 M, Fig.1. Perception of illness was most favorable at 2 years, at which time there was a slight decline in transmission frequency. Conclusions: Pt perception of HF was positively impacted during ambulatory hemodynamic monitoring including improvement in symptoms, less emotional effect of illness, improved sense of security and control over their HF throughout follow-up. This was associated with high-level pt adherence to pressure data transmission. The optimal level of chronic monitoring for stable pts to maintain clinical benefit while minimizing disease awareness beyond 2 years is still unknown.
Abstract 16339: Mitochondrial Function in Animal and Novel Human Disease Models of Tachycardiomyopathy
Authors: Michael G Paulus, Kathrin Renner, Steffen Pabel, Gabriela Pietrzyk, Andreas Luchner, Lars S Maier, Christoph M Birner, Katrin Streckfuß-Bömeke, Samuel T Sossalla, Alexander Dietl
Journal: Circulation (2020)

Introduction: Clinical significance of tachycardiomyopathy (TCM) increased with trials on catheter ablation therapy. Myocardial biopsies from patients show disturbed mitochondrial architecture. Hypothesis: TCM involves mitochondrial dysfunction. Methods: First, TCM was investigated in an animal model: pacemaker implantation in 7 rabbits was followed by tachypacing for 30 days (TCM), 7 animals served as sham-operated controls (SHAM). Second, results of the animal study were evaluated for their translational perspective for human disease using a novel model of induced pluripotent stem cell-derived cardiomyocytes (iPS-CM), derived from 4 healthy donors. IPS-CM were paced with 120 bpm (TACH) or 60 bpm (CTRL) for 7 days in vitro. Targeted transcriptomics, high-resolution respirometry and flow cytometry (MitoSOX Red) were performed. To account for variations between cell differentiations, experiments on iPS-CM were carried out in a paired design. Results: TCM showed LV dilatation and dysfunction (ΔLVEDD +5.3±0.2mm; ΔFS -19±8%; TCM-SHAM; p&lt;0.001). Histological findings resembled human disease entailing cardiomyocyte hypertrophy (CSA 519±32μm 2 vs. 413±21μm 2 , p&lt;0.01) without fibrosis (hydroxyproline content, p=0.52). Mitochondrial transcriptome of TCM was characterized by downregulation of 10 antioxidative enzymes (e.g. GPX3, fold change (FC) 0.4; TCM/SHAM; p&lt;0.05) as well as mitochondrial carriers, including ADP/ATP- and NADH-shuttling (SLC25A4, FC 0.7; SLC25A12, FC 0.8; p&lt;0.01). As transcriptomics implied impaired substrate import, respirometry was performed in whole tissue. In support of our findings on the transcriptome level, mitochondrial oxidative phosphorylation capacity decreased in TCM (133±13 vs. 170±16 pmol·O 2 ·s -1 ·mg -1 ·tissue, p&lt;0.05). Similarly, oxidative phosphorylation was reduced in iPS-CM (995±738 vs. 1838±901 pmolO 2 ·s -1 ·IU -1 citrate synthase activity, TACH vs. CTRL, p&lt;0.01). Concurrently, tachypacing increased mitochondrial superoxide emission in iPS-CM (MFI 491±206 vs. 301±119, p&lt;0.05). Conclusions: Persistent tachycardia alters two mitochondrial key functions in an animal and a novel human ex vivo model: oxidative phosphorylation capacity is reduced, while superoxide emission increases.
Abstract 14881: Impact of a Large-scale Telemedicine Network on Emergency Visits and Hospital Admissions During the Covid-19 Pandemic in Brazil: Data From the UNIMED-BH System
Authors: Bruno R Nascimento, Ana Cristina T Castro, Luiz Eduardo V Fróes, Antonio L Ribeiro, Cynthia B Araújo, Charles F Souza, Eduardo T Fróes, Luisa C Brant, Soraya D Souza
Journal: Circulation (2020)

Introduction: A strategy for healthcare surge control in the Covid-19 pandemic is forward triage by on-demand telemedicine (TM), implemented by several providers. We aimed to evaluate the impact of a large-scale Covid-19 TM system on visits to emergency medical services (EMS) and all-cause and cardiovascular (CV) hospital admissions during the pandemic in Brazil. Methods: From March 18 - May 18, 2020 we evaluated the database of UNIMED-BH, a cooperative Brazilian private health insurance, with over 1.25 million clients. The Covid-19 TM system consisted of: a) online mobile app with questions about Covid-19 symptoms, which redirects to teleconsultations in case of moderate/severe manifestations; b) telemonitoring system, with regular phone calls to all clients with reported flu-like symptoms or Covid-19 diagnosis, to monitor disease progression; c) 24/7 emergency call and ambulance system (GMOV), with VOIP triage and counselling by 2 physicians: calls with suspected Covid-19 or respiratory abnormalities were computed. EMS visits and admissions in all accredited hospitals were recorded, with diagnoses assessed by the Diagnosis Related Groups (DRG) method. Covid-19 lab diagnosis and deaths were identified from the patients’ registries, and outcomes assessed until June 1 st . Results: In 60 days, 24,351 patients (1.9% of clients) accessed one of the TM systems, 59% women, median age was 35±18 years. The most frequently utilized system was telemonitoring (16,717, 69%), followed by teleconsultation (13,350, 55%) and GMOV (683, 3%); 6,330 patients accessed multiple systems. The rates of EMS and hospital admissions for each system were: telemonitoring 19.7% (3,296) and 4.6% (774); teleconsultation 17.3% (2,312) and 2.3% (311) and GMOV: 55.9% (382) and 56.2% (384) patients. At total 4.1% (996) had at least 1 hospital admission, 32% (321) with respiratory diseases (41 requiring mechanical ventilation) and 5.6% (56) with CV diagnoses (12 acute coronary syndromes). Overall, 277 (1.1%) patients had confirmed Covid-19 diagnosis, and 160 (0.7%) died, 9 with Covid-19. Conclusion: The TM system resulted in low rates of EMS visits and hospital admissions, suggesting a positive impact on healthcare utilization. The percent of admissions due to CV causes was low.
Abstract 16762: Post-Operative Prognostic Prediction of Different Myocardial Fibrosis Measures in Severe Aortic Valvular Heart Disease
Authors: Lucas J Pires, Vitor E Rosa, THAMARA C MORAIS, Antonio S de Santis, Joao Ricardo C Fernandes, berta p boer, eduardo rossi, Paulo d Lavitola, Carlos E Rochitte, Cesar H Nomura, Pablo M Pomerantzeff, Flavio Tarasoutchi
Journal: Circulation (2020)

Introduction: Aortic stenosis (AS) and aortic regurgitation (AR) patients develop myocardial remodeling characterized by hypertrophia and fibrosis. Cardiac magnetic resonance (CMR) imaging can detect the presence of replacement myocardial fibrosis, by using late gadolinium enhancement (LGE), and diffuse myocardial fibrosis, by using extracellular volume (ECV) based measures (relative - ECV fraction - and absolute - indexed ECV) calculated from T1 mapping. There are only few studies with AS patients and scarce data with AR patients showing an association between fibrosis and post-operative clinical outcomes. Hypothesis: There is an association between preoperative myocardial fibrosis measures and post-operative clinical outcomes in severe aortic valvular heart disease (VHD) patients submitted to surgical intervention. Methods: Patients with isolated severe AS or AR were prospectively recruited to be submitted to CMR before indicated surgery, including LGE and ECV measures quantifications. All patients were submitted to conventional surgery and were followed during post-operative period. Results: The study population included 99 patients, 67 with AS and 32 with AR. After a median post-operative follow up of 12.3 (3.2-24.4) months, the presence of LGE areas, found in 32 patients (32.3%), independently predicted post-operative combined events (global mortality or STS morbidity events or persistent NYHA functional class III-IV) during follow up in univariate and multivariate Cox regression analyses (HR 3.96, 95%CI 1.76-8.91, p&lt;0.01). Kaplan-Meier curve is presented in Figure 1. ECV fraction (HR 1.02, 95%CI 0.96-1.09, p=0.55) or indexed ECV (HR 1.00, 95%CI 0.97-1.03, p=0.86) did not predict post-operative combined events. Conclusions: Presence of replacement myocardial fibrosis, but not diffuse myocardial fibrosis, in preoperative CMR predicts post-operative combined clinical events in severe VHD patients submitted to surgery.
Abstract 16704: Leukocyte Telomere Length and Risk of Stroke: The Strong Heart Family Study
Authors: Caroline Goode, Jinying Zhao, Richard B Devereux, Santosh Murthy, Alexander E Merkler, Parmanand Singh, Jason G Umans, Barbara V Howard, Shelley Cole, Amanda M Fretts, Lyle G Best, Tauqeer Ali, Elisa T Lee, Julie Stoner, Ying Zhang
Journal: Circulation (2020)

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.
Esophageal Motility Disorders and Gastroesophageal Reflux Disease
Authors: Ravinder Mittal, Michael F. Vaezi
Journal: New England Journal of Medicine (2020)

Esophageal motility disorders and esophageal reflux are common, produce a wide range of symptoms, and compromise quality of life. Neural and muscle-based mechanisms contribute to altered function of the lower esophageal sphincter, creating problems if it is too relaxed or too constricted. Improvements in diagnosis and treatment have improved the management of these disorders.
Abstract 16046: Conventional versus Right Mini-thoracotomy versus Robotic Mitral Valve Replacement/repair; Insights From a Network Meta-analysis
Authors: Yujiro Yokoyama, Hisato Takagi, Toshiki Kuno
Journal: Circulation (2020)

Background: Benefits and risks of minimally invasive cardiac surgery (MICS) through right mini-thoracotomy and robotic surgery for mitral valve are not fully understood. We conducted a network meta-analysis comparing the perioperative and long-term outcomes of mitral valve surgery via conventional sternotomy, MICS and robot. Methods: MEDLINE and EMBASE were searched through March 15th, 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated perioperative and long-term outcomes after mitral surgery via conventional sternotomy, MICS and robot. Subanalyses were conducted by restricting trials, in which mitral valve repair was tried first for all patients. Results: Our systematic literature search identified 2 RCTs and 21 PSM trials. MICS was related to significant decrease in PM ([RR] [95% confidence interval [CI] =0.56 [0.40-0.78]] and SSI (RR [95%CI] =0.53 [0.33-0.85) compared to conventional sternatomy. Re-exploration for bleeding was significantly higher in robot compared to sternotomy (RR [95% CI] =1.56 [1.03-2.37]), and transfusion was higher in sternotomy compared to MICS (RR [95%CI] =1.63 [1.27-2.08]). No significant differences were observed in perioperative mortality, MI, stroke, and LCOS among there procedures. Similarly, there were no significant differences in long-term survival and mitral valve reoperation. Suanalyses by restricting trials in which mitral valve repair tried first for all patients showed MICS was related to significant increase in mitral valve reoperation compared to conventional sternotomy (hazard ratio [95%CI] =7.33 [1.54-34.97]) (Figure). Conclusion: Our network meta-analysis demonstrated similar long-term survival and mitral valve reoperation. However, MICS was related to significant increase in mitral valve reoperation after mitral valve repair compared to conventional sternotomy.