Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Three-dimensional echocardiography of the athlete's heart: a comparison with cardiac magnetic resonance imaging.

Three-dimensional echocardiography (3DE) is the most accurate cardiac ultrasound technique to assess cardiac structure. 3DE has shown close correlation with cardiac magnetic resonance imaging (CMR) in various populations. There is limited data on the accuracy of 3DE in athletes and its value in detecting alterations during follow-up. Indexed left and right ventricular end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume, ejection fraction (LVEF, RVEF) and left ventricular mass (LVMi) were assessed by 3DE and CMR in two-hundred and one competitive endurance athletes (79% male) from the Pro@Heart trial. Sixty-four athletes were assessed at 2 year follow-up. Linear regression and Bland-Altman analyses compared 3DE and CMR at baseline and follow-up. Interquartile analysis evaluated the agreement as cardiac volumes and mass increase. 3DE showed strong correlation with CMR (LVEDVi r = 0.91, LVEF r = 0.85, LVMi r = 0.84, RVEDVi r = 0.84, RVEF r = 0.86 p < 0.001). At follow up, the percentage change by 3DE and CMR were similar (∆LVEDVi r = 0.96 bias - 0.3%, ∆LVEF r = 0.94, bias 0.7%, ∆LVMi r = 0.94 bias 0.8%, ∆RVESVi r = 0.93, bias 1.2%, ∆RVEF r = 0.87 bias 0.4%). 3DE underestimated volumes (LVEDVi bias - 18.5 mL/m2, RVEDVi bias - 25.5 mL/m2) and the degree of underestimation increased with larger dimensions (Q1vsQ4 LVEDVi relative bias - 14.5 versus - 17.4%, p = 0.016; Q1vsQ4 RVEDVi relative bias - 17 versus - 21.9%, p = 0.005). Measurements of cardiac volumes, mass and function by 3DE correlate well with CMR and 3DE accurately detects changes over time. 3DE underestimates volumes and the relative bias increases with larger cardiac size.

A Quality Improvement Approach to Decreasing Postdischarge Acute Care Reuse Among Children With Asthma.

OBJECTIVES: To reduce 7-day acute care reuse among children with asthma after discharge from an academic children's hospital by standardizing the delivery of clinical care and patient education. METHODS: A diverse group of stakeholders from our tertiary care children's hospital and local community agencies used quality improvement methods to implement a series of interventions within inpatient, emergency department (ED), and outpatient settings. These interventions were designed to improve admission, inpatient care, and discharge processes for children hospitalized because of asthma and included a focus on (1) resident education, (2) patient access to medication and asthma education, and (3) gaps in existing asthma clinical care pathways in the ED and ICU. The primary outcome was the rate of 7-day acute care reuse (combined hospital readmissions and ED revisits) after discharge from an index hospitalization for asthma, measured through a monthly review of electronic health record data and compared with a 6-month baseline period of reuse data. RESULTS: The mean 7-day reuse rate for asthma after discharge was 3.7% during the 6 months baseline period (n = 107) and 1.0% during the 15-month intervention period (n = 302). This included a shift in our median from 3.3% to 0% with an 8-month period of no 7-day reuse. CONCLUSIONS: An interprofessional quality improvement team successfully achieved and sustained a 73% reduction in mean 7-day asthma-related acute care reuse after discharge by standardizing provider training, care processes, and patient education.

Condensation Artifact.

During the ongoing COVID-19 pandemic, an artifact with hyperintense signal was observed on the brain images of a number of patients or research subjects, particularly those with heavy body weight and/or increased respiratory rate. The artifact was primarily seen on 3D or 2D sagittal or coronal T2-weighted images, although it occasionally also appeared in the axial plane. It manifested as a bright spot or a cluster of bright spots at similar locations, superior or lateral superior to the skull. This artifact was found to be caused by condensed water droplet(s) in the head coil as a consequence of the altered moisture flow pattern associated with each exhalation due to the mask on the patient. We call this artifact condensation artifact. Several strategies have been proposed to prevent or resolve the artifact. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Relation of Alcohol Consumption to Left Ventricular Fibrosis Using Cardiac Magnetic Resonance Imaging.

Light-to-moderate regular alcohol consumption has been associated with reduced mortality, heart failure, and sudden death, with a well described "U-shaped" relationship. We sought to determine whether markers of diffuse ventricular fibrosis as assessed by cardiac magnetic resonance imaging (CMR) T1 mapping differ between nondrinkers and regular drinkers. We prospectively recruited 165 participants to undergo 3T CMR ventricular T1 mapping which included 120 regular light-to-moderate drinkers (7 to 28 standard drinks per week for >12 months) and 45 age and gender-matched nondrinking controls (1 standard drink ∼12 g alcohol). Diffuse ventricular fibrosis was assessed using ShMOLLI T1 mapping sequences performed in mid-short axis. Native T1, postcontrast T1 times and extracellular volume were compared in the left ventricle between regular drinkers and lifelong nondrinkers. In total 165 participants (mean age 59 ± 12 years, 70% male, 36% hypertension, mean LVEF 58 ± 11%) underwent CMR. Moderate alcohol intake (mean alcohol intake 16 ± 6 SDs/week) was associated with lower markers of diffuse ventricular fibrosis: native T1 time 1140 ± 47 vs 1173 ± 39 ms, p < 0.001; postcontrast T1 time 470 ± 47 vs 445 ± 43 ms, p = 0.01; extracellular volume 25.0 ± 2.7% vs 27.0 ± 2.8%, p = 0.003 despite similar LV size (p = 0.55) and mass compared with nondrinkers (p = 0.78). Quantity of alcohol intake and beverage type did not predict lower native T1 times. In conclusion, light-to-moderate or "social" alcohol consumption is associated with T1 changes on CMR suggestive of a reduction in diffuse ventricular fibrosis. These preliminary findings may provide some insights into the association between modest alcohol intake and reduction in sudden death and heart failure.

Electrocardiographic Features Differentiating Arrhythmogenic Right Ventricular Cardiomyopathy From an Athlete's Heart.

OBJECTIVES: This study sought to compare electrocardiogram (ECG) variants in athletic and arrhythmogenic right ventricular cardiomyopathy (ARVC) cohorts matched for the confounders of age, sex, and ethnicity. BACKGROUND: Anterior T-wave inversion (TWIV1-V4) is a common electrocardiographic finding in both athletes and patients with ARVC, and is a frequent conundrum in the setting of pre-participation screening. J-point elevation (JPE) has been proposed as an accurate means of identifying athletes, whereas disease markers, including premature ventricular contractions (PVCs) and low-voltage signals, have been associated with ARVC. METHODS: This study examined 200 subjects with TWI V1-V4, including 100 healthy athletes and 100 ARVC patients matched 1:1 for age, sex, and ethnicity (age: 21 ± 5 years for athletes vs. 22 ± 5 years for ARVC patients; 47% male; 97% Caucasian). The presence of TWI, JPE, PVCs, and left ventricular hypertrophy (LVH) were assessed. RESULTS: JPE was observed in 27% of athletes versus 16% of ARVC patients (p = 0.09). Thus, JPE had poor specificity (27%) and accuracy (60%) in identifying healthy athletes. In contrast, ARVC patients demonstrated a greater prevalence of precordial TWI beyond lead V3 (34% vs. 8%; p < 0.001), inferior TWI (31% vs. 3%; p < 0.001), PVCs (18% vs. 0%; p < 0.001), and lower LVH scores (SV1 + RV5; 19 ± 1 mm vs. 30 ± 1 mm; p < 0.001). These combined factors provided more reliable differentiation between health and disease (specificity 82%, accuracy 81%). CONCLUSIONS: PVCs and low QRS voltages are more prevalent among ARVC patients than athletes, whereas JPE is a relatively poor discriminator of health and disease when the confounders of age, sex, and ethnicity are considered.

The Roles of Rods, Cones, and Melanopsin in Photoresponses of M4 Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) and Optokinetic Visual Behavior.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate not only image-forming vision like other ganglion cells, but also non-image-forming physiological responses to light such as pupil constriction and circadian photoentrainment. All ipRGCs respond to light through their endogenous photopigment melanopsin as well as rod/cone-driven synaptic inputs. A major knowledge gap is how melanopsin, rods, and cones differentially drive ipRGC photoresponses and image-forming vision. We whole-cell-recorded from M4-type ipRGCs lacking melanopsin, rod input, or cone input to dissect the roles of each component in ipRGCs' responses to steady and temporally modulated (≥0.3 Hz) lights. We also used a behavioral assay to determine how the elimination of melanopsin, rod, or cone function impacts the optokinetic visual behavior of mice. Results showed that the initial, transient peak in an M4 cell's responses to 10-s light steps arises from rod and cone inputs. Both the sustainability and poststimulus persistence of these light-step responses depend only on rod and/or cone inputs, which is unexpected because these ipRGC photoresponse properties have often been attributed primarily to melanopsin. For temporally varying stimuli, the enhancement of response sustainedness involves melanopsin, whereas stimulus tracking is mediated by rod and cone inputs. Finally, the behavioral assay showed that while all three photoreceptive systems are nearly equally important for contrast sensitivity, only cones and rods contribute to spatial acuity.

Gap-free segmentation of vascular networks with automatic image processing pipeline.

Current image processing techniques capture large vessels reliably but often fail to preserve connectivity in bifurcations and small vessels. Imaging artifacts and noise can create gaps and discontinuity of intensity that hinders segmentation of vascular trees. However, topological analysis of vascular trees require proper connectivity without gaps, loops or dangling segments. Proper tree connectivity is also important for high quality rendering of surface meshes for scientific visualization or 3D printing. We present a fully automated vessel enhancement pipeline with automated parameter settings for vessel enhancement of tree-like structures from customary imaging sources, including 3D rotational angiography, magnetic resonance angiography, magnetic resonance venography, and computed tomography angiography. The output of the filter pipeline is a vessel-enhanced image which is ideal for generating anatomical consistent network representations of the cerebral angioarchitecture for further topological or statistical analysis. The filter pipeline combined with computational modeling can potentially improve computer-aided diagnosis of cerebrovascular diseases by delivering biometrics and anatomy of the vasculature. It may serve as the first step in fully automatic epidemiological analysis of large clinical datasets. The automatic analysis would enable rigorous statistical comparison of biometrics in subject-specific vascular trees. The robust and accurate image segmentation using a validated filter pipeline would also eliminate operator dependency that has been observed in manual segmentation. Moreover, manual segmentation is time prohibitive given that vascular trees have more than thousands of segments and bifurcations so that interactive segmentation consumes excessive human resources. Subject-specific trees are a first step toward patient-specific hemodynamic simulations for assessing treatment outcomes.

Toward A New Evolutionary Synthesis.

This essay responds to Peter T. Saunders's call to go Beyond the neo-Darwinist Paradigm. While there is much to commend in his analysis, especially his suggestion that the extended evolutionary synthesis (EES) may not go far enough, he leaves the question of whether this should involve mere revision or total replacement open. A historiographical review reveals significant problems stemming from certain positivist assumptions and commitments within neo-Darwinian orthodoxy and the EES over and above any scientific considerations. As such, mere tweaking of the existing paradigm or its extension will do little to remedy the intellectual prejudices currently plaguing it. A complete overhaul is suggested by applying the López Ontological Demarcation Design (LODD) principle with biology in a multidisciplinary, non-reductionist philosophical framework. Building on the concept of Organismic-Systems Biology (OSB), a component of General Systems Theory (GTS) associated with polymathic biologist Ludwig von Bertalanffy (1901-1972), and cosmic evolution (CE) proposed by UCLA philosopher John Elof Boodin (1869-1950), the outline of a new evolutionary synthesis is offered as a prolegomenon to further study and evaluation.

Automatic recognition of subject-specific cerebrovascular trees.

PURPOSE: An image filter designed for reconstructing cerebrovascular trees from MR images is described. Current imaging techniques capture major cerebral vessels reliably, but often fail to detect small vessels, whose contrast is suppressed due to limited resolution, slow blood flow rate, and distortions around bifurcations or nonvascular structures. An incomplete view of angioarchitecture limits the information available to physicians. METHODS: A novel Hessian-based filter for contrast-enhancement in MR angiography and venography for blood vessel reconstruction without introducing dangling segments is presented. We quantify filter performance with receiver-operating-characteristic and dice-similarity-coefficient analysis. Total extracted vascular length, number-of-segments, volume, surface-to-distance, and positional error are calculated for validation. RESULTS: Reconstruction of cerebrovascular trees from MR images of six volunteers show that the new filter renders more complete representations of subject-specific cerebrovascular networks. Validation with phantom models shows the filter correctly detects blood vessels across all length scales without failing at bifurcations or distorting diameters. CONCLUSION: The novel filter can potentially improve the diagnosis of cerebrovascular diseases by delivering metrics and anatomy of the vasculature. It also facilitates the automated analysis of large datasets by computing biometrics free of operator subjectivity. The high quality reconstruction enables computational mesh generation for subject-specific hemodynamic simulations. Magn Reson Med 77:398-410, 2017. © 2016 Wiley Periodicals, Inc.

All spiking, sustained ON displaced amacrine cells receive gap-junction input from melanopsin ganglion cells.

Retinal neurons exhibit sustained versus transient light responses, which are thought to encode low- and high-frequency stimuli, respectively. This dichotomy has been recognized since the earliest intracellular recordings from the 1960s, but the underlying mechanisms are not yet fully understood. We report that in the ganglion cell layer of rat retinas, all spiking amacrine interneurons with sustained ON photoresponses receive gap-junction input from intrinsically photosensitive retinal ganglion cells (ipRGCs), recently discovered photoreceptors that specialize in prolonged irradiance detection. This input presumably allows ipRGCs to regulate the secretion of neuromodulators from these interneurons. We have identified three morphological varieties of such ipRGC-driven displaced amacrine cells: (1) monostratified cells with dendrites terminating exclusively in sublamina S5 of the inner plexiform layer, (2) bistratified cells with dendrites in both S1 and S5, and (3) polyaxonal cells with dendrites and axons stratifying in S5. Most of these amacrine cells are wide field, although some are medium field. The three classes respond to light differently, suggesting that they probably perform diverse functions. These results demonstrate that ipRGCs are a major source of tonic visual information within the retina and exert widespread intraretinal influence. They also add to recent evidence that ganglion cells signal not only to the brain.

Deep Venous Thrombosis with Pulmonary Embolism Related to IVIg Treatment: A Case Report and Literature Review.

IVIg therapy has potentially been related to arterial and venous therapy. We performed an Ovid review focusing on IVIg and thrombotic events. While a few case reports were reviewed case series and case control studies were particularly reviewed in relation to thrombotic events. Outcomes demonstrate a correlation between underlying cardiovascular risk factors with predominately arterial events which typically occurred within 4-24 hours of infusion. While venous events occurred less commonly they were associated with traditional risk factors and occurred later, typically, 1-7 days following infusion of IVIg. Potential causation of thrombotic events was discussed.

Training using simulation in internal medicine residencies: an educational perspective.

BACKGROUND: The American Board of Internal Medicine has defined through the min-CEX (Clinical Examination booklet) that a resident would need to perform anywhere from 3 to 5 procedures to be competent in a given procedure. Many faculty and residents believe that this number is too low to achieve competency. METHODS: Although simulation has been required as part of medical training, we have reviewed a number of articles addressing competence and potentially fewer complications with improved patient safety. RESULTS: The Accreditation Council for Graduate Medical Education has simply stated that simulation should be part of residency training. However, this has resulted in a disorganized approach among the nearly 385 internal medicine programs in the United States. CONCLUSIONS: This article suggests a model of simulation that addresses procedures, medical codes and major medical problems that each resident achieve competence in before graduating residency. This would require minimally a doubling of the number of procedures to define competency and will do so in a far more scientific method.

The 2014 United States National Residency Match Program data for primary care programs: a review.

The paper focuses on the past five years of National Residency Match Program (NRMP) information in the Unites States with a comparison point of twenty years ago utilized because of a referenced article. It is well known to our students going through the match that it is more competitive than in prior years. To rank enough programs for your field, take Step 2 early to maximize your score, to get quality letters and to practice mock interviews. The 99% match rate has remained steady over the past five years despite an increase in all primary care disciplines particularly Internal Medicine. Family Medicine and Internal Medicine work with, on average, about half U.S. seniors and half from other groups including Osteopathic and IMG (U.S. citizen and non-U.S. citizen). This can create a holistic experience for residents with a sharing of ideas from students from varied backgrounds. While the Supplemental Offer and Acceptance Program appear as an initial success, the student's goal should be to avoid such a step altogether. The key twenty years ago and today is the existence of appropriate numbers of resident and faculty role models. This is a stressful goal considering the demands on faculty for billing and patient care due to the shiftwork nature of the new work hours.

Alfred Russel Wallace's medical libertarianism: state medicine, human progress, and evolutionary purpose.

Alfred Russel Wallace (1823-1913), naturalist and explorer of South America and the Malay Archipelago, secured his place in history by independently discovering the theory of natural selection. His letter outlining the theory was sent from Ternate in eastern Indonesia and received at Down House, according to Charles Darwin (1809-82), on June 18, 1858, prompting the now-famed evolutionist to rush his languishing manuscript to press. Wallace's contributions to evolutionary biology, biogeography, and anthropology are well known, but his medical views have received far less attention. Within the context of a strident populist antivaccination movement and an ominous elitist eugenics campaign, Wallace took his stand, which revealed itself in a libertarianism that defended traditional socialist constituencies (the working poor, the lumpenproletariat, and feminist reformers) against state-mandated medical interventions. Rather than viewing Wallace as a heterodox contrarian, this article argues that his positions were logical outgrowths of his medical libertarianism and evolutionary and social theories.