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Over the last 50 years, access to new data and analytical tools has expanded the study of analytical paleobiology, contributing to innovative analyses of biodiversity dynamics over Earth's history. Despite—or even spurred by—this growing availability of resources, analytical paleobiology faces deep-rooted obstacles that stem from the need for more equitable access to data and best practices to guide analyses of the fossil record. Recent progress has been accelerated by a collective push toward more collaborative, interdisciplinary, and open science, especially by early-career researchers. Here, we survey four challenges facing analytical paleobiology from an early-career perspective: (1) accounting for biases when interpreting the fossil record; (2) integrating fossil and modern biodiversity data; (3) building data science skills; and (4) increasing data accessibility and equity. We discuss recent efforts to address each challenge, highlight persisting barriers, and identify tools that have advanced analytical work. Given the inherent linkages between these challenges, we encourage discourse across disciplines to find common solutions. We also affirm the need for systemic changes that reevaluate how we conduct and share paleobiological research.

Supplementary tables for Dillon et al. Paleobiology:Challenges and directions in analytical paleobiology Abstract:Over the last 50 years, access to new data and analytical tools has expanded the study of analytical paleobiology, contributing to innovative analyses of biodiversity dynamics over Earth’s history. Despite—or even spurred by—this growing availability of resources, analytical paleobiology faces deep-rooted obstacles that stem from the need for more equitable access to data and best practices to guide analyses of the fossil record. Recent progress has been accelerated by a collective push toward more collaborative, interdisciplinary, and open science, especially by early career researchers. Here, we survey four challenges facing analytical paleobiology from an early career perspective: (1) accounting for biases when interpreting the fossil record; (2) integrating fossil and modern biodiversity data; (3) building data science skills; and (4) increasing data accessibility and equity. We discuss recent efforts to address each challenge, highlight persisting barriers, and identify tools that have advanced analytical work. Given the inherent linkages between these challenges, we encourage discourse across disciplines to find common solutions. We also affirm the need for systemic changes that reevaluate how we conduct and share paleobiological research. This article is accompanied by two supplementary tables.For each, we provide a .csv file and a formatted .xlsx file. Supplementary Table 1. Examples of databases and online data portals used for paleobiological and (paleo)ecological research, along with their primary temporal, spatial, and taxonomic scope. N/A indicates that the corresponding information was either not applicable, undefined, or not readily available. The 'Modern' time period refers to last ~400 years unless otherwise specified. File names: Supplementary Table 1_Dillon et al. Paleobiology_2022.csv Supplementary Table 1 formatted_Dillon et al. Paleobiology_2022.xlsx Supplementary Table 2. Examples of programming packages and tools that are commonly used to analyze and visualize paleo data. Tools are grouped by their primary functionality. File names: Supplementary Table 2_Dillon et al. Paleobiology_2022.csv Supplementary Table 2 formatted_Dillon et al. Paleobiology_2022.xlsx Supplementary References. Full references for articles and software cited in the supplementary tables can be found in the supplementary references. File names: Supplementary References_Dillon et al. Paleobiology_2022.txt

Cardiovascular disease is the leading cause of mortality among breast cancer survivors. Anthracyclines and trastuzumab have been associated with an increased risk of cardiotoxicity, requiring close follow-up for signs of clinical heart failure or asymptomatic left ventricular systolic dysfunction. Whether neurohormonal antagonism with angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blockers (ARBs), or β-blockers can prevent the development of chemotherapy-induced cardiomyopathy in this population remains unknown. We studied 459 women who were diagnosed with breast cancer at our medical center from January 2014 to December 2021 and evaluated baseline characteristics, oncologic treatment, and outcomes. The primary end point was the development of cardiotoxicity, defined as symptomatic decline in ejection fraction of ≥5% below 55% or an asymptomatic decline of ≥10% after treatment with chemotherapy. Patients who were exposed to neurohormonal antagonists were more likely to have hypertension, hyperlipidemia, and diabetes. There was an increased risk of cardiotoxicity noted for patients who were older (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01 to 1.1), smokers within the past 10 years (HR 2.54, 95% CI 1.41 to 4.6), or who received a combination of both trastuzumab and anthracycline therapy (HR 2.52, 95% CI 1.01 to 6.3). Over a median follow-up of 12 months, there were no significant protective benefits noted for patients who were taking ACE-I/ARBs (HR 0.49, 95% CI 0.17 to 1.4), β-blockers (HR 0.50, 95% CI 0.16 to 1.6), or both (HR 1.30, 95% CI 0.44 to 3.9). In conclusion, previous use of ACE-I/ARBs and β-blockers, separately or in combination, was not associated with a reduction in the development of cardiotoxicity in patients receiving anthracycline or trastuzumab therapies. Older age, smoking, and combination chemotherapy were found to be associated with an increased risk.

Background: Cardiac toxicity (CT) in the form of left ventricular systolic dysfunction is a well-known complication of anti-HER2 therapy. Prior clinical trial data has suggested potential factors associated with increased risk for CT. We sought to develop a clinical risk prediction model from real world patients to better identify patients who may be at higher risk for CT. Methods: Patients treated with anti-HER2 agents at all Mayo Clinic sites from Jan 2008 to July 2015 were reviewed. Patient data including age, race, body mass index, comorbidities, smoking history, baseline ejection fraction (EF), presence of left ventricular hypertrophy (LVH), prior cancer treatments, number of anti-HER2 agents used, and cardiac medication use were recorded. Factors were compared in patients with and without development of CT. Cox regression models were used to identify univariate and multivariate predictors of CT. A risk score was then assigned based on the final multivariable model. Results: 604 patients were included in final analysis. Median follow-up 2.9 yrs; median age: 57 yr; baseline EF: 64%. One yr CT rate was 7%. Independent predictors of CT were age, baseline EF, LVH, and anthracycline use (C index=0.74). Based on model coefficient, scores of 1, 1, 2 and 3 were assigned to age>55, EF Table 1. Multivariable Cox regression model predicting cardiac dysfunctionParameterParameter EstimateHR (95%CI)p valueScoreAge >550.909552.48(1.27, 4.84)0.00751EF Citation Format: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia. A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-14.

Introduction Doxorubicin is an anthracycline used as a chemotherapeutic drug for the treatment of a wide range of adult and pediatric cancers. Doxorubicin is associated with an increased risk of cardiomyopathy and heart failure with up to 10% of patients developing cardiac complications. A GWAS conducted of 1,191 patients from the N9831 clinical trial identified that cardiac gene expression and genetic variants of TRPC6 were associated with a decline in left ventricular ejection fraction (LVEF) (p=0.005 and p=1.6x10–6, respectively). TRPC6 is a non-selective cation channel expressed in heart and vascular tissue. TRPC6 participates in the pathogenesis of cardiac hypertrophy as a pathological response to chronic mechanical stress. Chronic activation has been found to promote cardiac fibrosis leading to heart failure. Purpose TRPC6 variants could be associated with increased risk of doxorubicin-induced cardiotoxicity. Data/tests to determine which patients may progress to cardiomyopathy and heart failure are currently lacking and there are no targeted treatments to prevent cardiomyopathy in these patients. Methods In preliminary in vivo data, B6.129 wild-type mice or TRPC6 knockout mice were treated with either 6x intraperitoneal saline or 4mg/kg doxorubicin injections (cumulative dose of 24mg/kg). Results We found doxorubicin increased cardiac vacuolation (male, p≤0.001 and female, p≤0.05) in WT mice compared to controls. Higher HW/BW ratio was observed in male TRPC6 knock out mice compared to wild-type mice when both were treated with doxorubicin (males, p=0.005 and females, p=0.19). Additionally, we found that doxorubicin-induced cardiac injury was significantly reduced in TRPC6 knock-out mice compared to wild-type mice based on reduced vacuolation (p=0.0004 males, p=0.03 females), with the effect being greater in male mice than female mice. Furthermore, a significant decrease in stroke volume (p=0.007), diastolic volume (p=0.01) and cardiac output (p=0.004) in wild-type male mice treated with doxorubicin compared to control and TRPC6 knock-out mice. Our in vitro preliminary data show that inhibition of TRPC6 using the TRPC6 inhibitor GsMTx-4 in human iPSC-derived cardiomyocytes significantly reduced doxorubicin-induced apoptosis (p Conclusion TRPC6 could be a novel therapeutic target in the prevention of chemotherapy-induced cardiomyopathy and heart failure. Additionally genetic mapping of TRCP6 functional variants may provide a new screening tool to determine increased risk of developing heart failure. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic

A 61-year-old male presented for an annual exam and received a transthoracic echocardiogram (TTE) which revealed a mobile mass arising from a subaortic membrane. Further investigations with a transesophageal echocardiogram (TEE) and cardiac computerized tomography angiography (CTA) confirmed the presence of a mobile 9 mm×3 mm mass on a subaortic membrane. Cardiothoracic surgery was performed with an open operation removing the mass and subaortic membrane. Upon visual inspection, the mass was likened to a sea anemone and immunohistochemical staining performed pathologically confirmed the diagnosis of cardiac papillary fibroelastoma. This case represents the first reported example of a cardiac papillary fibroelastoma (PFE) arising from a subaortic membrane. Although PFEs are benign cardiac tumors, proper identification and consideration for excision of these lesions may be indicated to prevent thromboembolic complications.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Summary Peroxisomes are metabolic organelles that perform a diverse array of critical functions in human physiology. Traditional isolation methods for peroxisomes can take more than 1 h to complete and can be laborious to implement. To address this, we have now extended our prior work on rapid organellar isolation to peroxisomes via the development of a peroxisomally localized 3XHA epitope tag (“PEROXO-Tag”) and associated immunoprecipitation (“PEROXO-IP”) workflow. Our PEROXO-IP workflow has excellent reproducibility, is easy to implement, and achieves highly rapid (~10 min post homogenization) and specific isolation of human peroxisomes, which we characterize here via proteomic profiling. By offering speed, specificity, reproducibility, and ease of use, the PEROXO-IP workflow should facilitate studies on the biology of peroxisomes., Graphical Abstract, Highlights • Our “PEROXO-Tag” is a peroxisomally localized 3XHA epitope tag • The companion “PEROXO-IP” workflow enables anti-HA immunoisolation of peroxisomes • The isolated peroxisomes can be utilized for downstream analyses, such as proteomics • The PEROXO-IP workflow is rapid (~10 min), specific, reproducible, and easy to use, Biological Sciences; Biochemistry Methods; Cell Biology; Methodology in Biological Sciences

Objectives The use of continuous pulse oximetry (CPOX) is ubiquitous among hospitalized patients, despite limited evidence that it improves clinical outcomes. The objective of this study was to reduce the use of CPOX among hospitalized patients in the nonintensive care unit and nonprogressive care unit settings. Methods This interventional trial included the creation a new local guideline for CPOX use and subsequent staff education. CPOX use, patient acuity, hospital length of stay, and code blue events were measured before and after the intervention. Results Postintervention there was a clinically significant and sustained decrease in CPOX use of 18% over 1 year. There were no significant changes postintervention in hospital length of stay or number of code blue events. Conclusions Development of a guideline for CPOX use and staff education successfully led to a decrease in CPOX use, without an increase in hospital length of stay or code blue events.

Echocardiography is the most common imaging modality for assessment of the right ventricle in patients with pulmonary arterial hypertension (PAH). Echocardiographic parameters were identified as independent risk factors for mortality in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) and other PAH cohorts. We sought to identify readily obtained echocardiographic features associated with PAH survival.Retrospective analysis of 175 patients with Group 1 was performed. Baseline clinical and laboratory assessment including REVEAL risk criteria were obtained and standard 2-Dimensional and Doppler echocardiography performed at baseline was reviewed. Univariate and multivariate analyses of echocardiographic parameters were performed. Estimated right atrial pressure15 mmHg (HR 2.39, P = .02), tricuspid regurgitation ≥ moderate (HR 2.16, P = .04), and presence of pericardial effusion (HR 1.8, P = .05) were identified as independent, high-risk echocardiographic features in PAH. A validation cohort of 677 patients was identified and Kaplan-Meier survival analysis was performed in both cohorts. High-risk echocardiographic features stratified survival curves of both cohorts (P.01 for all). The presence of 3 high-risk echocardiographic features greatly increased risk of 1-year (RR 4.86) and 3-year (RR 3.35) mortality (P.05 for both).Estimated right atrial pressure15, tricuspid regurgitation ≥ moderate, and presence of pericardial effusion are high-risk echocardiographic features in PAH. When seen in combination, these features greatly increase risk of mortality in PAH and may lead to more timely enhanced therapy for patients identified as having an increased risk for death.

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing.

Objectives: Pulmonary arterial hypertension (PAH) is a deadly disease without any effective cure. Identification of the PAH-associated gut microbiome may shift conceptual paradigms of the disease that could lead to new therapeutic advancement. We tested the hypothesis that PAH patients have distinct gut microbiome composition contributing to PAH that predicts the disease. Methods: A total of 71 participants were recruited. Fecal microbiomes of 18 type 1 PAH patients (mean pulmonary arterial pressure [mPAP] 57.4±16.7 mmHg) and 13 reference subjects were compared by shotgun metagenomics methods. Plasma from 22 PAH patients (mPAP 48.3± 18.4 mmHg) and 18 reference subjects was used in untargeted metabolomic analysis. Results: Significant taxonomic and functional changes in the microbiome of the PAH cohort were observed. PAH patients had increased gut barrier dysfunction and inflammation as evidenced by plasma markers and metagenomics. A random forest model predicted PAH from gut microbiome composition with 82.6% accuracy. Changes in the gut microbiome were associated with purine metabolism, arginine biosynthesis, trimethylamine production and tryptophan biosynthesis, all previously associated with PAH. Area under the curve of the multi-variate receiver operating characteristics (ROC) plot for metabolites of these pathways had a predictive accuracy of 0.965. Conclusions: The gut microbiome/metabolites of PAH patients predict disease in random forest models and ROC analyses. The unique PAH gut microbiome influences carnitine, arginine and purine metabolisms contributing to pathophysiology. These highlight previously unknown roles of gut bacteria and their metabolites in PAH that could lead to new therapeutic or management paradigms.

Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of greater efficacy but unfortunately not of greater safety. In fact, a broad spectrum of toxicities can be seen with targeted therapies, including cardiovascular toxicities. Among these, cardiomyopathy and heart failure have received greatest attention, given their profound implications for continuation of cancer therapies and cardiovascular morbidity and mortality. Prediction of risk has always posed a challenge and even more so with the newer targeted agents. The merits of accurate risk prediction, however, are very evident, e.g. facilitating treatment decisions even before the first dose is given. This is important for agents with a long half-life and high potential to induced life-threatening cardiac complications, such as myocarditis with immune checkpoint inhibitors. An opportunity to address these needs in the field of cardio-oncology is provided by the expanding repertoire of “-omics” and other tools in precision medicine and their integration in a systems biology approach. This may allow for new insights into patho-mechanisms and the creation of more precise and cost-effective risk prediction tools with the ultimate goals of improved therapy decisions and prevention of cardiovascular complications. Herein, we explore this topic as a future approach to translating the complexity of cardio-oncology to the reality of patient care.

Introduction: Our study assesses the utility of telemetry in identifying decompensation in patients with documented cardiopulmonary arrest. Methods: A retrospective review of inpatients who experienced a cardiopulmonary arrest from May 1, 2008, until June 30, 2014, was performed. Telemetry records 24 hours prior to and immediately preceding cardiopulmonary arrest were reviewed. Patient subanalyses based on clinical demographics were made as well as analyses of survival comparing patients with identifiable rhythm changes in telemetry to those without. Results: Of 242 patients included in the study, 75 (31.0%) and 110 (45.5%) experienced telemetry changes at the 24-hour and immediately preceding time periods, respectively. Of the telemetry changes, the majority were classified as nonmalignant (n = 50, 66.7% and n = 66, 55.5% at 24 hours prior and immediately preceding, respectively). There was no difference in telemetry changes between intensive care unit (ICU) and non-ICU patients and among patients stratified according to the American Heart Association telemetry indications. There was no difference in survival when comparing patients with telemetry changes immediately preceding and at 24 hours prior to an event (n = 30, 27.3% and n = 15, 20.0%) to those without telemetry changes during the same periods (n = 27, 20.5% and n = 42, 25.2%; P = .22 and .39). Conclusion: Telemetry has limited utility in predicting clinical decompensation in the inpatient setting.

Early detection of mild pulmonary arterial hypertension (PAH) based on clinical evaluation and echocardiography remains quite challenging. In addition to enhanced right ventricular (RV) assessment, cardiac magnetic resonance (CMR) imaging may accurately reflect deleterious remodeling and increased stiffness of the central pulmonary arteries based on pulsatility, or percent change of the PA during the cardiac cycle. The purpose of this study is to assess the utility of measuring PA pulsatility by CMR as a potential early maker in PAH. We hypothesize that pulsatility may help discriminate mild PAH from normal control subjects. Consecutive patients with PAH (n = 51) were prospectively enrolled to receive same day CMR and right heart catheterization (RHC). PA stiffness indices including pulsatility, distensibility, compliance, and capacitance were calculated. Comparisons were made between patients with varying severities of PAH and normal controls (n = 18). Of the 51 subjects, 20 had mild PAH, and 31 moderate-severe based on hemodynamic criteria. PA pulsatility demonstrated a progressive decline from normal controls (53%), mild PAH (22%), to moderate-severe PAH (17%; p

Introduction: Pulmonary arterial hypertension (PAH) is a fatal disease and vasodilators are the mainstay for its therapy. However, they offer restricted advancement opportunities for the control and treatment of PAH. Thus, the PAH field needs a paradigm-shifting strategy for its successful management and control. Objective: To test the hypothesis that gut microbial dysbiosis and its increased permeability are associated with PAH. Methods: Healthy control subjects and patients with PAH were recruited from two hospitals in the Americas to ascertain the wider applicability of our hypothesis. Fecal samples of PAH patients (n=19) and control, reference subjects (n=16) were obtained at the Hospital de Clinicas de Porto Alegre, Brazil, for microbiota analysis. Plasma/serum samples were collected from PAH patients (n=22) and control, reference subjects (n=19) at the Mayo Clinic, Jacksonville, Florida, USA, for analysis of gut leakiness and inflammatory biomarkers. Results: In PAH patients, a significant decrease in abundance, diversity and evenness of gut microbial population was observed as measured by 16S ribosomal DNA analyses of fecal samples. Analysis of fecal bacteria populations also demonstrated significant increases in gram-positive, facultative-anaerobic genera, such as Actinomyces, Bifidobacterium Slackia, and Streptococcus in PAH patients. Further, plasma zonulin and iFABP, the biomarkers for gut leakiness increased by 40.3% (p=0.0018) and 81% (p=0.0012), respectively in PAH patients. High plasma LPS, HMGB1, and TIMP1 levels are involved in increased gut inflammation and gut mucosal injury. We also observed LPS, HMGB1, and TIMP1 levels were increased by 363% (p=0.0096), 20.5% (p=0.0027), and 213% (p Conclusions: PAH patients demonstrate profound gut microbial dysbiosis and increased permeability and inflammation. Further characterization of PAH specific microbial species holds novel management potential with the use of pre- and probiotics, designer antibiotics, appropriate fecal/bacterial transplantation, on top of background proven therapies.

Essentials VWF multimers have an established association with valvular heart disease.Significant interlaboratory variation exists in VWF multimeric analysis.We describe a method to normalize VWF multimers for assessment of cardiac lesion severity and clinical bleeding.Normalized VWF multimer ratios improved the diagnostic capabilities of the assay. Background von Willebrand factor (VWF) multimer quantitation has been utilized in the assessment of valvular heart disease, however, there is no standardized method for quantitation. We compared three methods of assessment which utilized a normal plasma control. Methods We analyzed 476 samples and their control plasma from 368 patients with valvular heart disease, hypertrophic cardiomyopathy, or LVAD therapy, and 27 normal subjects. VWF multimers were assessed as normalized VWF multimer ratios (NMR) of gel bands >15/2‐15 (NMR15) or gel bands >10/2‐10 (NMR10). Associations of VWF laboratory and multimeric assessments with cardiac lesion severity and acquired bleeding were investigated. Results Abnormal multimers were present in 78% of patients with moderate to severe hemodynamic abnormalities compared to 19% of patients with normal or mildly abnormal hemodynamics. NMR showed strong association with severe cardiac lesions (NMR15: OR 15.29, CI 9.04‐27.18; NMR10: OR 14.18, CI 8.88‐23.21). PFA‐CADP was strongly associated with moderate to severe cardiac lesions (OR 14.91, CI 9.08‐24.50). PFA‐CADP and NMR15 showed excellent ability to discriminate ≥moderate (AUC 0.86, CI 0.83‐0.89 and 0.83, CI 0.79‐0.87 respectively) and severe cardiac lesions (AUC 0.84, CI 0.81‐0.88 and 0.85, CI 0.81‐0.88 respectively). NMR was less strongly associated with bleeding (OR 4.01 for NMR10, CI 2.49‐6.58). Conclusion Quantification of VWF multimers may provide clinical utility in circumstances where clinical estimation of cardiac lesion severity is challenging, such as with dysfunctional prosthetic valves. The presence of abnormal VWF multimers is associated with bleeding, however further quantitation provided only modest improvement in risk stratification.

In recent years, several novel anticoagulants have been approved for the prevention of thromboembolic strokes as an alternative to warfarin in patients with atrial arrhythmias. Studies have evaluated these medications in patients undergoing radiofrequency ablation, yet no data exists to evaluate the bleeding risk in patients undergoing cryoballoon ablation procedures. Patients that underwent either cryoballoon ablation alone or with additional radiofrequency ablation over the past 3 years were included in the study. Patients were stratified into one of three subsets based on type of anticoagulation (warfarin, dabigatran, or rivaroxaban). Bleeding complications during the first 48 h and first 2 weeks following the ablation were recorded. Major complications were defined as hemorrhage requiring blood products or need for vascular intervention. Minor complications included prolonged bleeding from catheter insertion site, development of ecchymosis, or hematoma formation. Intraprocedural activated clotting times (ACT) were assessed and compared. A total of 217 patients met inclusion criteria of which 87 (40.1 %) patients were on warfarin, 90 (41.5 %) patients on dabigatran, and 40 (18.4 %) patients on rivaroxaban. The overall bleeding complication rate was 12.0 %. All complications occurred within the first 48 h post-ablation. Nine (10.3 %) complications occurred in the warfarin subset, ten (11.1 %) in the rivaroxaban subset, and seven (17.5 %) in the dabigatran subset (p = 0.49). The warfarin and dabigatran subsets had higher average ACT levels (424.9 versus 406.5) compared to the rivaroxaban subset (393.4; p

Despite improvements in post-operative outcomes, patients with cirrhotic liver disease undergoing orthotopic liver transplantation (OLT) continue to experience major adverse cardiac events (MACE). Use of routine stress testing and coronary angiography is common prior to OLT, however, the utility of

Cardiac magnetic resonance (CMR) imaging in pulmonary arterial hypertension (PAH) may aid in assessment of right ventricular (RV) morphology and function as well as contractile reserve (RVCR). Previous data suggests that RVCR may be diminished in patients with PAH patients by bicycle ergometer (eCMR

Little data exists evaluating how different risk factors influence outcomes following in-hospital arrests.A retrospective review of patients that suffered a cardiopulmonary arrest between 1 May 2008 and 30 June 2014 was performed. Patients were stratified into subsets based on cardiac versus non-cardiac reasons for admission.199 patients met inclusion criteria, of which 138 (69.3%) had a non-cardiac reason for admission and 61 (30.7%) a cardiac etiology. No difference in demographics and non-cardiac comorbidities were present. Cardiac-related comorbidities were more prevalent in the cardiac etiology subset. Arrests with a shockable rhythm were more common in the cardiac group (P0.0001), yet return of spontaneous circulation from the index event was similar (P = 0.254). More patients in the cardiac group were alive at 24-h post resuscitation (n = 34, 55.7% versus n = 49, 35.5%; P = 0.0085), discharge (n = 21, 34.4% versus n = 19, 13.8%; P = 0.0018), and at last follow-up (n = 13, 21.3% versus n = 14, 10.1%; P = 0.0434).Although patients with cardiac and non-cardiac etiologies for admission have similar rates of return of spontaneous circulation, those with cardiac etiologies are more likely to survive to hospital discharge and outpatient follow-up.

Delivery of medical care is evolving rapidly worldwide. Over the past several years in the USA, there has been a rapid shift in reimbursement from a simple fee-for-service model to more complex models that attempt to link payment to quality and value. Change in any large system can be difficult, but with medicine, the transition to a value-based system has been particularly hard to implement because both quality and cost are difficult to quantify. Professional societies and other medical groups are developing different programs in an attempt to define high value care. However, applying a national standard of value for any treatment is challenging, since value varies from person to person, and the individual benefit must remain the central tenet for delivering best patient-centered medical care. Regardless of the specific operational features of the rapidly changing healthcare environment, physicians must first and foremost always remain patient advocates.

Advanced cardiovascular life support guidelines exist, yet there are variations in clinical practice. Our study aims to describe the utilization of medications during resuscitation from in-hospital cardiopulmonary arrest. A retrospective review of patients who suffered a cardiopulmonary arrest from May 2008 to June 2014 was performed. Clinical and resuscitation data, including timing and dose of medications used, were extracted from the electronic medical record and comparisons made. A total of 94 patients were included in the study. Patients were divided into different groups based on the medication combination used during resuscitation: (1) epinephrine; (2) epinephrine and bicarbonate; (3) epinephrine, bicarbonate, and calcium; (4) epinephrine, bicarbonate, and epinephrine drip; and (5) epinephrine, bicarbonate, calcium, and epinephrine drip. No difference in baseline demographics or clinical data was present, apart from history of dementia and the use of calcium channel blockers. The number of medications given was correlated with resuscitation duration (Spearman's rank correlation = 0.50, p0.001). The proportion of patients who died during the arrest was 12.5% in those who received epinephrine alone, 30.0% in those who received only epinephrine and bicarbonate, and 46.7% to 57.9% in the remaining groups. Patients receiving only epinephrine had shorter resuscitation durations compared to that of the other groups (p0.001) and improved survival (p = 0.003). In conclusion, providers frequently use nonguideline medications in resuscitation efforts for in-hospital cardiopulmonary arrests. Increased duration and mortality rates were found in those resuscitations compared with epinephrine alone, likely due to the longer resuscitation duration in the former groups.

In mammals, the cytosine in CG dinucleotides is typically methylated producing 5-methylcytosine (5mC), a chemically less stable form of cytosine that can spontaneously deaminate to thymidine resulting in a T•G mismatched base pair. Unlike other eukaryotes that efficiently repair this mismatched base pair back to C•G, in mammals, 5mCG deamination is mutagenic, sometimes producing TG dinucleotides, explaining the depletion of CG dinucleotides in mammalian genomes. It was suggested that new TG dinucleotides generate genetic diversity that may be critical for evolutionary change. We tested this conjecture by examining the DNA sequence properties of regulatory sequences identified by DNase I hypersensitive sites (DHSs) in human and mouse genomes. We hypothesized that the new TG dinucleotides generate transcription factor binding sites (TFBS) that become tissue-specific DHSs (TS-DHSs). We find that 8-mers containing the CG dinucleotide are enriched in DHSs in both species. However, 8-mers containing a TG and no CG dinucleotide are preferentially enriched in TS-DHSs when compared with 8-mers with neither a TG nor a CG dinucleotide. The most enriched 8-mer with a TG and no CG dinucleotide in tissue-specific regulatory regions in both genomes is the AP-1 motif ( TG: A(C)/GT CA: N), and we find evidence that TG dinucleotides in the AP-1 motif arose from CG dinucleotides. Additional TS-DHS-enriched TFBS containing the TG/CA dinucleotide are the E-Box motif (G CA: GC TG: C), the NF-1 motif (GG CATG: CC), and the GR (glucocorticoid receptor) motif (G-A CATG: T-C). Our results support the suggestion that cytosine methylation is mutagenic in tetrapods producing TG dinucleotides that create TFBS that drive evolution.

A man in his 60s presented to the emergency department with chest pain. He had a history of hypertension but no other cardiac history.His painwasdescribedas adull ache localized tohis epigastrium; it hadbeenconstant for4hours, didnot radiate, andwasnot exacerbated by exertion. Examination of the heart, lungs, and abdomen had normal results. A chest x-ray revealed no acute cardiopulmonary process. An electrocardiogram (ECG)was obtained and is shown in Figure 1. Question:What is the underlying rhythm?

Introduction Code status discussions are important during a hospitalization, yet variation in its practice exists. No data have assessed the likelihood of patients to change code status following a cardiopulmonary arrest. Methods A retrospective review of all patients that experienced a cardiopulmonary arrest between May 1, 2008 and June 30, 2014 at an academic medical center was performed. The proportion of code status modifications to do not resuscitate (DNR) from full code was assessed. Baseline clinical characteristics, resuscitation factors, and 24-h post-resuscitation, hospital, and overall survival rates were compared between the two subsets. Results A total of 157 patients survived the index event and were included. One hundred and fifteen (73.2%) patients did not have a change in code status following the index event, while 42 (26.8%) changed code status to DNR. Clinical characteristics were similar between subsets, although patients in the change to DNR subset were older (average age 67.7 years) compared to the full code subset (average age 59.2 years; p = 0.005). Patients in the DNR subset had longer overall resuscitation efforts with less attempts at defibrillation. Compared to the DNR subset, patients that remained full code demonstrated higher 24-h post-resuscitation (n = 108, 93.9% versus n = 32, 76.2%; p = 0.001) and hospital (n = 50, 43.5% versus n = 6, 14.3%; p = 0.001) survival rates. Patients in the DNR subset were more likely to have neurologic deficits on discharge and shorter overall survival. Conclusions Patient code status wishes do tend to change during critical periods within a hospitalization, adding emphasis for continued code status evaluation.

Despite technical limitations, transthoracic echocardiography (TTE) is the most commonly used imaging modality for right ventricular assessment in patients with pulmonary arterial hypertension (PAH). Recent studies have demonstrated the utility of cardiac magnetic resonance (CMR) imaging in the

Background Coronary artery vasospasm after administration of fluorouracil (5-FU) is a rare complication. Commonly presenting as chest pain during or shortly after 5-FU infusions, vasospasm can place patients at risk for ventricular dysrhythmia, myocardial ischemia, and infarction. Although not fully understood, any 5-FU cardiotoxicity seems to be multifactorial, and patients with coronary artery disease and renal dysfunction may be at particular risk. Case Report A 46-year-old woman with no prior cardiovascular disease history presented with sudden-onset chest pain after initial administration of 5-FU continuous infusion therapy. The patient subsequently developed ventricular fibrillation arrest and underwent successful electrocardioversion. Coronary angiography was unremarkable for coronary stenosis or vasospasm. The presumed etiology was secondary to 5-FU cardiac toxicity. The patient was re-challenged with 5-FU therapy and developed repeat chest pain. The 5-FU was completely stopped and the patient's symptoms resolved, with no further dysrhythmic events 9 months after initial presentation. Why Should an Emergency Physician Be Aware of This? Patients who develop chest pain during or after 5-FU infusion should warrant strong consideration for admission and continuous cardiac monitoring for potential ventricular dysrhythmias and cardiac ischemia.