Citations

We present a case series that highlights the diagnostic challenges with left ventricular hypertrophy (LVH) and left ventricular outflow tract obstruction (LVOTO). Fixed structural lesions causing LVOTO with secondary LVH may mimic hypertrophic obstructive cardiomyopathy (HOCM). Management of these two entities is critically different. Misdiagnosis and failure to recognize fixed left ventricular outflow tract (LVOT) lesions may result in morbidity as a result of inappropriate therapy and delay of definitive surgical treatment. It is thus necessary to identify the correct type and level of obstruction in the LVOT by careful correlation of clinical examination, Doppler evaluation, and advanced imaging findings.

Background The mechanisms of atrial fibrillation (AF) are highly divergent. The prevalence of AF increases significantly with age, and underling mechanisms might vary with age. Endothelial dysfunction may be associated with AF and atrial arrhythmia recurrence after catheter ablation. We tested the hypothesis that the impact of endothelial dysfunction on arrhythmia recurrence following catheter ablation is age dependent. Methods and Results This study enrolled 92 participants with AF undergoing catheter ablation. Endothelial function was assessed by peripheral arterial tonometry before ablation, and the natural logarithmic transformation of reactive hyperemia index was calculated. Endothelial dysfunction was defined as a natural logarithmic transformation of reactive hyperemia index <0.618 (median). Participants were followed for atrial tachycardia, flutter, and fibrillation recurrence for a median of 14 months. The mean age was 57±10 years. There was significant interaction between age and endothelial dysfunction in association with recurrence of AF ( P =0.029) and any atrial arrhythmia ( P =0.015), and the risk associated with endothelial dysfunction for arrhythmia recurrence was higher in younger versus older participants. Participants were divided into 2 age groups at a threshold of 60 years. Among participants aged ≤60 years, multivariate Cox proportional hazards analysis revealed the independent association between endothelial dysfunction and increased risk of arrhythmia recurrence (hazard ratio for AF 4.18 [95% CI 1.33–15.82], P =0.014, and for any atrial arrhythmia 3.62 [95% CI 1.29–11.81], P =0.014). Kaplan–Meier analysis showed that participants with endothelial dysfunction had significantly higher rates of recurrence of AF ( P =0.01) and any atrial arrhythmia ( P =0.002). Conclusions The risk associated with endothelial dysfunction for arrhythmia recurrence following catheter ablation was age dependent and was higher in younger participants.

AbstractObjectivesRapid response teams (RRTs) respond to signs of deterioration to avoid morbidity and mortality. Early RRT activation (eRRT) in patients admitted from the emergency department (ED) is associated with significantly increased mortality. Predicting these events may represent an opportunity to identify patients who would benefit from further resuscitation, aid disposition decision‐making, or improve communication between ED and inpatient providers. We aimed to create a clinical prediction instrument to quantify the risk of eRRT.MethodsWe performed an observational cohort study of patients admitted to a non–intensive care unit (ICU) setting who triggered eRRT from January 2009 to December of 2012 compared to those who did not trigger eRRT. Age, sex, ED vital sign measurements, and final ED diagnosis by ICD‐9 code were evaluated in a multivariable logistic regression model. The performance of prediction models was assessed using discrimination summarized by area under a receiver operating curve (AUC) and calibration with the Hosmer and Lemeshow goodness‐of‐fit test. The final model was used to create a simplified scoring system.ResultsThe eRRT group consisted of 474 patients who were compared to 2,575 patients in the reference group. Age and sex did not add significant discrimination to the model and were eliminated from the simplified, final model. This model, which included vital signs and diagnosis category, was found to have an AUC of 0.754 (95% confidence interval [CI] = 0.730 to 0.778) and was used to create a simplified scoring system. The odds ratio for the association of a 1‐unit increase in risk score with eRRT was 1.37 (95% CI = 1.32 to 1.41; p < 0.001). When internally validated, the score was found to have an AUC of 0.759 (95% CI = 0.735 to 0.753). Calculated scores ranged from −3 to 18, which corresponded to predicted probabilities of eRRT ranging from 5.1% to 72.2%.ConclusionsIn summary, the PeRRT score is a simple tool that can be referenced by emergency providers at the bedside to quantify the risk of early RRT activation and potential deterioration, helping to answer the question, “How likely is my patient to trigger an RRT activation in the next twelve hours?” Given that patients who trigger eRRT have an elevated risk of morbidity and mortality, higher scores should result in resuscitative intervention, further observation in the ED, consideration of ICU admission, or direct enhanced communication between ED and inpatient providers. A prospective multicenter study is required to further validate this instrument.

AbstractBackgroundLittle is known about the optimal use of shared decision making (SDM) to guide palliative and end‐of‐life decisions in the emergency department (ED).ObjectiveThe objective was to convene a working group to develop a set of research questions that, when answered, will substantially advance the ability of clinicians to use SDM to guide palliative and end‐of‐life care decisions in the ED.MethodsParticipants were identified based on expertise in emergency, palliative, or geriatrics care; policy or patient‐advocacy; and spanned physician, nursing, social work, legal, and patient perspectives. Input from the group was elicited using a time‐staggered Delphi process including three teleconferences, an open platform for asynchronous input, and an in‐person meeting to obtain a final round of input from all members and to identify and resolve or describe areas of disagreement.ConclusionKey research questions identified by the group related to which ED patients are likely to benefit from palliative care (PC), what interventions can most effectively promote PC in the ED, what outcomes are most appropriate to assess the impact of these interventions, what is the potential for initiating advance care planning in the ED to help patients define long‐term goals of care, and what policies influence palliative and end‐of‐life care decision making in the ED. Answers to these questions have the potential to substantially improve the quality of care for ED patients with advanced illness.

AbstractMigraine is one of the world's most common neurological disorders. Current acute migraine treatments have suboptimal efficacy, and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective, but small molecule antagonists have not been advanced because of toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel “druggable” target for inhibiting CGRP release and for potential relevance for treatment of migraine pain. Collapsin response mediator protein 2 has been demonstrated to regulate N-type voltage-gated Ca2+channel activity and Ca2+-dependent CGRP release in sensory neurons. The coexpression of CRMP2 with N-type voltage-gated Ca2+channel and CGRP in trigeminal ganglia (TGs) sensory neurons suggested the possibility of a novel approach to regulate CGRP release in the trigeminal system. Screening protocols surprisingly revealed that (S)-lacosamide ((S)-LCM), an inactive analog of the clinically approved small molecule antiepileptic drug (R)-lacosamide (Vimpat), inhibited CRMP2 phosphorylation by cyclin-dependent kinase 5 in rat TG slices and decreased depolarization-evoked Ca2+influx in TG cells in culture. (S)-LCM significantly blocked capsaicin-evoked CGRP release from dural nerve terminals in the rat in ex vivo cranial cup preparation. Additionally, cephalic and extracephalic cutaneous allodynia induced in rats by activation of dural nociceptors with a cocktail of inflammatory mediators, was inhibited by oral administration of (S)-LCM. The confirmation of CRMP2 as an upstream mediator of CGRP release, together with the brain penetrance of this molecule suggests (S)-LCM as a potential therapy for acute migraine.

ABSTRACT Economic and societal pressures influence modern medical practice to develop and implement prevention strategies. Anterior cruciate ligament (ACL) injury devastates the knee joint leading to short term disability and long term sequelae. Due to the high risk of long term osteoarthritis in all treatment populations following ACL injury, prevention is the only effective intervention for this life‐altering disruption in knee health. The “Sequence of Prevention” Model provides a framework to monitor progress towards the ultimate goal of preventing ACL injuries. Utilizing this model, our multidisciplinary collaborative research team has spent the last decade working to delineate injury mechanisms, identify injury risk factors, predict which athletes are at‐risk for injury, and develop ACL injury prevention programs. Within this model of injury prevention, modifiable factors (biomechanical and neuromuscular) related to injury mechanisms likely provide the best opportunity for intervention strategies aimed to decrease the risk of ACL injury, particularly in female athletes. Knowledge advancements have led to the development of potential solutions that allow athletes to compete with lowered risk of ACL injury. Design and integration of personalized clinical assessment tools and targeted prevention strategies for athletes at high risk for ACL injury may transform current prevention practices and ultimately significantly reduce ACL injury incidence. This 2016 OREF Clinical Research Award focuses on the authors’ work and contributions to the field. The author's acknowledge the many research groups who have contributed to the current state of knowledge in the fields of ACL injury mechanisms, injury risk screening and injury prevention strategies. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1843–1855, 2016.

Objectives: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. Design: A retrospective cohort study. Setting: A tertiary-care medical center. Patients: High-risk adult ICU patients from October 2008 to December 2010. Interventions: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson’s correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. Measurements and Main Results: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57–77) years, 28 (24–34) kg/m2, and 1.9 (1.7–2.2) m2, respectively. The mean (± sd) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r 2) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (–1 d for each 10 unit of sarcopenia index [95% CI, –1.4 to –0.2; p = 0.006]). Conclusions: The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.

Abstract Rationale Despite significant advances in knowledge of the genetic architecture of asthma, specific contributors to the variability in the burden between populations remain uncovered. Objectives To identify additional genetic susceptibility factors of asthma in European American and African American populations. Methods A phenotyping algorithm mining electronic medical records was developed and validated to recruit cases with asthma and control subjects from the Electronic Medical Records and Genomics network. Genome-wide association analyses were performed in pediatric and adult asthma cases and control subjects with European American and African American ancestry followed by metaanalysis. Nominally significant results were reanalyzed conditioning on allergy status. Measurements and Main Results The validation of the algorithm yielded an average of 95.8% positive predictive values for both cases and control subjects. The algorithm accrued 21,644 subjects (65.83% European American and 34.17% African American). We identified four novel population-specific associations with asthma after metaanalyses: loci 6p21.31, 9p21.2, and 10q21.3 in the European American population, and the PTGES gene in African Americans. TEK at 9p21.2, which encodes TIE2, has been shown to be involved in remodeling the airway wall in asthma, and the association remained significant after conditioning by allergy. PTGES, which encodes the prostaglandin E synthase, has also been linked to asthma, where deficient prostaglandin E2 synthesis has been associated with airway remodeling. Conclusions This study adds to understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.