Search

Aorto-atrial fistula is a rare and life-threatening complication of infective endocarditis, classically diagnosed by visualizing a connection between the aorta and atrium with associated continuous flow. A patient presented with bioprosthetic and native valve enterococcal endocarditis with multiple complications, including an aorto-atrial fistula that was diagnosed by color M-mode on transesophageal echocardiography. We review the features of aorto-atrial fistula and utilize this case to demonstrate how M-mode can be leveraged to provide improved temporal resolution in the setting of diagnostic uncertainty.

Background Heart failure with preserved ejection fraction ≥50% is prevalent with few evidence‐based therapies. In a trial of patients with heart failure with preserved ejection fraction with specialized pacemakers, treatment with accelerated personalized pacing averaging 75 bpm (myPACE) markedly improved quality of life, NT‐proBNP (N‐terminal pro–brain natriuretic peptide), physical activity, and atrial fibrillation burden compared with the standard lower rate setting of 60 bpm (usual care). Methods and Results In this exploratory study, provider‐initiated echocardiographic studies obtained before and after the trial were assessed for changes in left ventricular (LV) structure and function among participants who continued their pacing assignment. The analytic approach aimed to detect differences in standard and advanced echocardiographic parameters within and between study arms. Of the 100 participants, 16 myPACE and 20 usual care arm had a qualifying set of echocardiograms performed a mean (SD) 3 (2.0) years apart. Despite similar baseline echocardiogram measures, sustained exposure to moderately accelerated pacing resulted in reduced septal wall thickness (in cm: myPACE 1.1 [0.2] versus usual care 1.2 [0.2], P=0.008) and lower LV mass to systolic volume ratio (in g/mL: myPACE 4.8 [1.9] versus usual care 6.8 [3.1], P=0.038) accompanied by a minor reduction in LV ejection fraction (in %: myPACE 55 [5] versus usual care 60 [5], P=0.015). These changes were paralleled by improvements in heart failure‐related quality of life (myPACE Minnesota Living with Heart Failure Questionnaire improved by 16.1 [13.9] points, whereas usual care worsened by 6.9 [11.6] points, P

Abstract Background Obtaining research funding support is integral to a successful career in science. Training and practice in grant writing, as well as engagement in peer review of grant applications may help lead to successful research funding. However, there is little evidence on the impact of institutional programs on the career development of early career investigators (ECIs). Objectives Understand the impact of participation in an institutional research award program on the career development of ECIs. Methods The Cardiovascular Research Institute of Vermont established an Early Career Research (ECR) award program in 2018. ECIs who participated as applicants or reviewers in the first 3 years of the program (2018‐2020) were surveyed to understand the impact of the ECR award program on their grant writing and professional development. Results Ninety‐four percent of 17 applicants and 90% of 19 reviewers completed the survey. Ninety‐two percent of funded and 75% of unfunded applicants, and 87% of reviewers reported that the program was beneficial to their professional development. Similarly, 85% of funded applicants, 75% of unfunded applicants, and 80% of reviewers reported improvement in their grant‐writing skills. All respondents reported they would recommend the ECR award program to their peers. Conclusions This single‐institution ECR award program had a positive impact on ECI’s professional development and grant‐writing skills and may lead to further extramural funding opportunities.

Patient experience is a core component of the Institute for Healthcare Improvement Triple Aim for health care improvement. Although resident physicians must meet quality improvement (QI) competencies prior to graduation, QI training during residency may not adequately prepare residents to improve patient and family experience. We describe an active learning QI curriculum engaging 3 Patient and Family Advisors as partners alongside 15 resident physicians. This partnership proved to be a meaningful experience for both groups, with the development of mutual respect and insight into the contributions that patients and families bring to solving problems in health care quality.

Pankaj Jogi, Tom Overend, John Kramer School of Physical Therapy, University of Western Ontario, London, ON, Canada Background: Information available in the literature on clinically based and laboratory-based outcome measures of balance is limited. How much information is provided by clinically based outcome measures compared to laboratory-based measure in patients with total hip (THA) and knee arthroplasty (TKA) is not known. Aim: The purpose of this study was to determine the relationship between selected clinically based outcome measures and laboratory-based force platform measure in patients following THA and TKA. Methods: Patients who underwent THA (n = 26) and TKA (n = 28) were evaluated at about 5–7 weeks following surgery. Participants were assessed using four clinically based outcome measures – 1) the Berg Balance Scale (BBS), 2) the Timed Up and Go test (TUG), 3) the Activities-specific Balance Confidence Scale (ABC), and 4) the Western Ontario McMaster Universities Osteoarthritis Index-function subscale (WOMAC-function) – and one laboratory-based force plate measure (95% ellipse area). Results: Moderate correlations were observed between the BBS and the 95% ellipse area of force plate (r = 0.46–0.51) for the two-legged stance, the anterior lean stance, and the posterior lean stance. Fair correlations were observed between TUG and the 95% ellipse area of force plate (r = 0.31–0.37) for all the three test conditions. Low correlations were observed for the ABC and the WOMAC-function with the 95% ellipse area of force plate (r = 0.11–0.25) for all the three test conditions. Conclusion: The BBS demonstrated the greatest correlations with the 95% ellipse area of the force plate measure and should be preferred by physical therapists over the TUG, the ABC, and the WOMAC-function to assess balance in patients with THA and TKA. Keywords: total knee arthroplasty, total hip arthroplasty, force plate, clinical measures, balance

A 76-year-old male with metastatic renal carcinoma on day 24 of pazopanib was admitted with complaints of emesis, confusion, and hematuria. Laboratory testing showed acute kidney injury, hyperbilirubinemia, and thrombocytopenia. Scattered schistocytes were seen on peripheral smear, and he was diagnosed with thrombotic microangiopathy (TMA). He was started on daily, one-volume plasma exchange with rapid improvement in thrombocytopenia. ADAMTS13 activity returned as undetectably low with no inhibitor detected. After cessation of plasmapheresis, repeat ADAMTS13 activity returned as normal. Unfortunately, his platelet count started to downtrend within four days after developing septicemia thought to be due to a catheter-associated infection. He was placed on comfort care measures after discussion with his family. An autopsy listed the major cause of death as metastatic renal cell carcinoma. According to two separate systematic reviews, there have been no cases of proven drug-induced TMA where decreased ADAMTS13 activity was the identified mechanism. While pazopanib is also associated with TMA, this unique case suggests a novel potential mechanism for TMA associated with pazopanib and brings forth “drug-induced thrombotic thrombocytopenic purpura” that quickly responds to plasmapheresis as a possible new diagnostic entity requiring prompt recognition and treatment.

BackgroundGenome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations.MethodsA total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using receiver operating characteristic curves and by analysis of the distribution of PRS.ResultsEuropean ancestry subjects with higher than median PRSs were at greater risk for onset of AUD than subjects with lower than median PRSs (p = 3 × 10-7). Area under the curve for the receiver operating characteristic analysis peaked at 0.88 to 0.95 using PRS plus sex, family history, comorbid disorders, age at first drink, and peer drinking; predictive power was primarily driven by clinical variables. In this high-risk sample, European ancestry subjects with a PRS score in the highest quartile showed a 72% risk for developing AUD and a 35% risk of developing severe AUD (compared with risks of 54% and 16%, respectively, in the lowest quartile).ConclusionsPredictive power for PRSs in the extremes of the distribution suggests that these may have future clinical utility. Uncertainties in interpretation at the individual level still preclude current application.

Massive binary evolution models are needed to predict massive star populations in star-forming galaxies, the supernova diversity, and the number and properties of gravitational wave sources. Such models are often computed using so-called rapid binary evolution codes, which approximate the evolution of the binary components based on detailed single star models. However, about one-third of the interacting massive binary stars undergo mass transfer during core hydrogen-burning (Case A mass transfer), whose outcome is difficult to derive from single star models. For this work, we used a large grid of detailed binary evolution models for primaries in the initial mass range 10–40 M⊙ with a Large and Small Magellanic Cloud composition, to derive analytic fits for the key quantities needed in rapid binary evolution codes, that is, the duration of core hydrogen-burning, and the resulting donor star mass. We find that systems with shorter orbital periods produce up to 50% lighter stripped donors and have a lifetime up to 30% larger than wider systems. Both quantities strongly depend on the initial binary orbital period, but the initial mass ratio and the mass-transfer efficiency of the binary have little impact on the outcome. Our results are easily parameterisable and can be used to capture the effects of Case A mass transfer more accurately in rapid binary evolution codes. [ABSTRACT FROM AUTHOR]

Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case-control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10(-7)) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.

Aorto-atrial fistula is a rare and life-threatening complication of infective endocarditis, classically diagnosed by visualizing a connection between the aorta and atrium with associated continuous flow. A patient presented with bioprosthetic and native valve enterococcal endocarditis with multiple complications, including an aorto-atrial fistula that was diagnosed by color M-mode on transesophageal echocardiography. We review the features of aorto-atrial fistula and utilize this case to demonstrate how M-mode can be leveraged to provide improved temporal resolution in the setting of diagnostic uncertainty. [ABSTRACT FROM AUTHOR]

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.

Context. Blazar AO 0235+164, located at a redshift of z = 0.94, has undergone several sharp multi-spectral-range flaring episodes over recent decades. In particular, the episodes that peaked in 2008 and 2015, which were subject to extensive multi-wavelength coverage, exhibited an interesting behavior. Aims. We study the actual origin of these two observed flares by constraining the properties of the observed photo-polarimetric variability as well as of the broadband spectral energy distribution and the observed time-evolution behavior of the source. We use ultra-high-resolution total-flux and polarimetric very-long-baseline interferometry (VLBI) imaging. Methods. The analysis of VLBI images allowed us to constrain kinematic and geometrical parameters of the 7 mm jet. We used the discrete correlation function to compute the statistical correlation and the delays between emission at different spectral ranges. The multi-epoch modeling of the spectral energy distributions allowed us to propose specific models of the emission; in particular, with the aim to model the unusual spectral features observed in this source in the X-ray region of the spectrum during strong multi spectral-range flares. Results. We find that these X-ray spectral features can be explained by an emission component originating in a separate particle distribution than the one responsible for the two standard blazar bumps. This is in agreement with the results of our correlation analysis, where we did not find a strong correlation between the X-ray and the remaining spectral ranges. We find that both external Compton-dominated and synchrotron self-Compton-dominated models are able to explain the observed spectral energy distributions. However, the synchrotron self-Compton models are strongly favored by the delays and geometrical parameters inferred from the observations. [ABSTRACT FROM AUTHOR]

Aim: Emerging evidence suggests a beneficial effect of higher heart rates in some patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the impact of higher backup pacing rates in HFpEF patients with preexisting pacemaker systems that limit pacemaker‐mediated dyssynchrony across left ventricular (LV) volumes and LV ejection fraction (LVEF). Methods and results: This is a post‐hoc analysis of the myPACE clinical trial that evaluated the effects of personalized accelerated pacing setting (myPACE) versus standard of care on changes in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), pacemaker‐detected activity levels, and atrial fibrillation (AF) burden in patients with HFpEF with preexisting pacemakers. Between‐treatment comparisons were performed using linear regression models adjusting for the baseline value of the exposure (ANCOVA design). This study included 93 patients with pre‐trial transthoracic echocardiograms available (usual care n = 49; myPACE n = 44). NT‐proBNP levels and MLHFQ scores improved in a higher magnitude in the myPACE group at lower indexed LV end‐diastolic volumes (iLVEDV) (NT‐proBNP–iLVEDV interaction p = 0.006; MLHFQ–iLVEDV interaction p = 0.068). In addition, personalized accelerated pacing led to improved changes in activity levels and NT‐proBNP, especially at higher LVEF (activity levels–LVEF interaction p = 0.009; NT‐proBNP–LVEF interaction p = 0.058). No evidence of heterogeneity was found across LV volumes or LVEF for pacemaker‐detected AF burden. Conclusions: In the post‐hoc analysis of the myPACE trial, we observed that the benefits of a personalized accelerated backup pacing on MLHFQ score, NT‐proBNP, and pacemaker‐detected activity levels appear to be more pronounced in patients with smaller iLVEDV and higher LVEF. [ABSTRACT FROM AUTHOR]