Cardiology Commons^™

A Curious Case Of Intermittent Left Bundle Branch Block Associated With Cough, Hunaina Shahab, Osman Faheem, Kumail Khandwala, Aamir Hameed

Section of Cardiology

A handful of cases of voluntary control of left bundle branch block (LBBB) have been described in the literature. We report the case of a middle-aged man who was found to have LBBB on baseline electrocardiogram (ECG) which disappeared on coughing and then reappeared with the same maneuver. Subsequent myocardial perfusion scan showed reduced count in the anteroseptal region likely attributed to LBBB. It is possible that the intermittent conduction changes may be due to the alteration in the vagal tone associated with cough as reflected in the change in the PR interval on the ECG.

Outcome Of Radioactive Iodine Therapy In Toxic Nodular Goiter In Pakistan, Tauseef Ahmad, Adeel Khoja, Naveed Rashid, Muhammad Areeb Ashfaq

Section of Cardiology

Objective: To determine the outcome of patients receiving radioactive iodine therapy for toxic nodular goiter coming to Aga Khan University Hospital Karachi.

Methods: A total of 89 patients who visited the outpatient department of Aga Khan University Hospital from January 2010 to August 2017 were recruited for the study. Toxic nodular goiter was diagnosed on the basis of having hot nodule on thyroid scan with low TSH and high FT4/T4. Other demographic and laboratory data were also recorded.

Results: Eighty nine patients with toxic nodular goiter received a dose range from 10 to 30mCi RAI. Six months after RAI, 36.2% …

Sleep Fainting: A Neurocardiogenic Entity, Hunaina Shahab, Ambreen A. Sonawalla, Maryam Khan, Aman Qureshi

Section of Cardiology

Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for hospital admissions. Classic teaching is that upright posture is a prerequisite for vagally mediated syncope (VMS) and that syncope in the supine position has more sinister causes. We present five patients, three males and two females, with a mean age of 44.4 (range 29-67) years, who presented with VMS in the supine position (sleep fainting). Four patients also had a history of classic upright syncope. Based on their clinical features and thorough investigations, we excluded other …

Short-Term Association Between Black Carbon Exposure And Cardiovascular Diseases In Pakistan’S Largest Megacity, Daniel Malashock, Haider Khwaja, Zafar Fatmi, Azhar Siddique, Yi Lu, Shao Lin, David Carpenter

Community Health Sciences

This study investigated the association between black carbon (BC) exposure and hospital admissions (HAs) and outpatient department/emergency room (OPD/ER) visits for cardiovascular diseases (CVD) among residents of Karachi, the largest city in Pakistan. We measured daily concentrations of BC in fine particulate matter (PM2.5) and collected records of HAs and OPD/ER visits for CVD from 2 major tertiary care hospitals serving Karachi for 6 weeks continuously during each quarter over 1 year (August 2008–August 2009). We subsequently analyzed daily counts of hospital and BC data over 0–3 lag days. Daily mean BC concentrations varied from 1 to 32 µg/m3 . …

Wearable Cardioverter-Defibrillator After Myocardial Infarction, Jeffrey E. Olgin, Mark J. Pletcher, Eric Vittinghoff, Jerzy Wranicz, Rajesh Malik, Daniel P. Morin, Steven Zweibel, Alfred E. Buxton, Claude S. Elayi, Eugene H. Chung, Eric Rashba, Martin Borggrefe, Trisha F Hue, Carol Maguire, Feng Lin, Joel A. Simon, Stephen Hulley, Byron K. Lee, Vest Investigators

Gill Heart & Vascular Institute Faculty Publications

BACKGROUND

Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter–defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter–defibrillator would reduce the incidence of sudden death during this high-risk period is unclear.

METHODS

We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter–defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from …

Takotsubo Cardiomyopathy Associated With Polycythemia Vera., Sijan Basnet, Priya Rajagopalan, Rashmi Dhital, Biswaraj Tharu

Reading Hospital Internal Medicine Residency

Takotsubo cardiomyopathy is characterized by transient apical ballooning with preserved basal ventricular function triggered by physical or emotional stressors. We present a case of a 75-year-old man referred to our facility for the management of acute myocardial infarction later diagnosed as takotsubo cardiomyopathy. We believe platelet-mediated adrenaline release from massive thrombocytosis might have been the precipitating factor for the pathogenesis of takotsubo cardiomyopathy.

Left Ventricular Mechanical Dyssynchrony For Cad Diagnosis: Does It Have Incremental Clinical Values?, Zhixin Jiang, Weihua Zhou

Faculty Publications

No abstract provided.

Comparison Of Left Ventricular Strains And Torsion Derived From Feature Tracking And Dense Cmr, Gregory J. Wehner, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Jing Chen, Sean M. Hamlet, Jared A. Feindt, Walter Dimitri Mojsejenko, Mark A. Fogel, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Cardiovascular magnetic resonance (CMR) feature tracking is increasingly used to quantify cardiac mechanics from cine CMR imaging, although validation against reference standard techniques has been limited. Furthermore, studies have suggested that commonly-derived metrics, such as peak global strain (reported in 63% of feature tracking studies), can be quantified using contours from just two frames – end-diastole (ED) and end-systole (ES) – without requiring tracking software. We hypothesized that mechanics derived from feature tracking would not agree with those derived from a reference standard (displacement-encoding with stimulated echoes (DENSE) imaging), and that peak strain from feature tracking would agree with …

Effects Of Beta Blockers And Ace Inhibitors After Left Ventricular Assist Device Implantation, Gaurang Vaidya, Emma Birks, Jessica Pillarella, Benjamin Salgado, Rajakrishnan Vijayakrishnan, Andrew Lenneman, Mark Slaughter, Dmitry Abramov

The VAD Journal

Purpose: While Beta blockers(BB) and Angiotensin system blockers(ACEinh/ARB) are important components in advanced heart failure therapy, their use after left ventricular assist device (LVAD) implantation remains controversial. Concern has been raised about possible adverse effects of BB on right ventricular(RV) function while tolerance and efficacy/outcome data for ACEinh are lacking. This study aimed to characterize the use of medical therapy post-LVAD implantation and to evaluate its safety and efficacy. Methods: Demographic, clinical and echocardiographic variables of patients implanted with a continuous-flow LVAD between 2012 and 2015 at a single center were retrospectively reviewed. Mortality and heart failure(CHF) hospitalizations were followed …

Transcriptional Up-Regulation Of Relaxin-3 By Nur77 Attenuates Β-Adrenergic Agonist-Induced Apoptosis In Cardiomyocytes., Xiaohua You, Zhifu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun

Center for Translational Medicine Faculty Papers

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 …

Bivalirudin Anticoagulation Dosing Protocol For Extracorporeal Membrane Oxygenation: A Retrospective Review., Jared W. Netley Pharmd, Mpa , Bcps, James Roy Pharmd, Joseph Greenlee Iii Md, Shaun Hart Np, Michael Todt Pharmd, Bryan Statz Pharmd

Parkview Pharmacy Department

Anticoagulation with unfractionated heparin during extracorporeal membrane oxygenation (ECMO) is common, but alternative agents are being evaluated for safety and efficacy. The objective of this analysis was to assess if a comprehensive bivalirudin dosing and monitoring protocol effectively guides dose adjustments and monitoring of bivalirudin in patients during ECMO. Our analysis included 11 patients who received bivalirudin during ECMO therapy and had dosing managed using our hospital derived protocol. Patients treated over a 1-year period were included in this retrospective analysis. Clinical characteristics and changes in activated partial thromboplastin time (aPTT) were evaluated from medical records to determine the efficacy …

A Patient-Centered Approach Towards Designing A Novel Cied Remote Monitoring Report, Michael J. Mirro, Romisa Rohani Ghahari, R Ahmed, Lauren Reining, Shauna Wagner, Gavin Lehmann, Jaime Heller, Melissa Omlor, Tammy Toscos

Presentations and Events

Objective: We sought to identify the CIED remote monitoring device report content for delivery to patients via a Personal Health Record that encompasses all available device data and is responsive to user information needs and preferences.

Conclusions: 1. Patients do not wish to receive all RM data 2. Interested in receiving device activity and cardiac episode data 3. Not interested in device settings or information 4. Shared preferences are useful for a novel patient-centered RM report 5. Current study extends our previous work confirming the patient desire for RM data

Antiphosphatidylserine Antibody As A Cause Of Multiple Dural Venous Sinus Thromboses And St-Elevation Myocardial Infarction, Chelsea K. Varner, Caillin W. Marquardt, Peter V. Pickens

Student Papers, Posters & Projects

Objective: Rare disease Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antibodies directed against phos-pholipids on plasma membranes. Through unclear mechanisms, APS confers hypercoagulability. APS may cause recurrent thromboses in the arterial and venous vasculature. We report a case of primary APS resulting in cerebral venous thrombosis and ST-elevation myocardial infarction (STEMI) for which only antiphosphatidylserine (aPS) IgM antibody was positive after extensive investigation. Case Report: A 48-year-old male was admitted after a witnessed generalized seizure with subsequent confusion. Imaging demonstrated thrombosis of multiple central nervous system (CNS) sinuses, including the superior sagittal sinus and bilateral transverse sinuses. …

Bevacizumab: A Rare Cause Of Nonischemic Cardiomyopathy., Oreoluwa Oladiran, Salik Nazir

Reading Hospital Internal Medicine Residency

Left ventricular dysfunction is a rare side effect of bevacizumab occurring in 2-4% of cases. We report the case of a 68-year-old woman who presented to the emergency department (ED) with sudden onset of shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. She was tachypneic and in respiratory distress. Physical examination revealed jugular venous distention, diffuse expiratory wheeze, and bipedal edema. She had been started on bevacizumab for the treatment of hereditary hemorrhagic telangiectasia 1 month prior to presentation. Laboratory tests revealed BNP of 1697 pg/ml with slightly elevated troponin 0.05 ng/ml. Chest X-ray showed interstitial edema with cardiomegaly, and …

Overcoming Small Data Limitations In Heart Disease Prediction By Using Surrogate Data, Alfeo Sabay, Laurie Harris, Vivek Bejugama, Karen Jaceldo-Siegl

SMU Data Science Review

In this paper, we present a heart disease prediction use case showing how synthetic data can be used to address privacy concerns and overcome constraints inherent in small medical research data sets. While advanced machine learning algorithms, such as neural networks models, can be implemented to improve prediction accuracy, these require very large data sets which are often not available in medical or clinical research. We examine the use of surrogate data sets comprised of synthetic observations for modeling heart disease prediction. We generate surrogate data, based on the characteristics of original observations, and compare prediction accuracy results achieved from …

Heparin Bridging Therapy Is Not Necessary For Patients With Atrial Fibrillation Undergoing Temporary Interruption Of Warfarin Therapy For Elective Invasive Procedures Or Surgery, Shannon Paquette

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. New Engl J Med. Aug 2015;373(9):823-833. doi: 10.1056/NEJMoa1501035

First Case Start Times For Vascular Surgery, Timothy Kafer, Brian Nolan, Jill Knutson, Amy Fournier, Lori Luebbert, J Gregoire, M Daigle, M E. Souliere, J Colpitts, E Anderson, P Briggs, L Ramsey, R Pratt-Pooler, M Maclean, E Estes, S Cheney, D Buck, B Rioux, L Marles

MaineHealth Maine Medical Center

Problem/Impact Statement:

85% of first cases at Maine Medical Center for Vascular Surgery start late. According to one study done by Aurora Health Care; of 5,500 first case surgeries, 88% of them started late. The impact of this is far reaching. It is not in alignment with MMC value of Patient Centered Care because the patient becomes dissatisfied waiting to be brought in to surgery , they are fasting for longer than anticipated, and being away from their family while they wait causing anxiety. The financial impact is $1995 for each 1⁄2 hr. of O.R. time. Furthermore, this may result …

Electrocardiographic Characteristics, Antiarrhythmic Utilization, And Outcomes In Patients With Left Ventricular Assist Devices, Scott Lundgren, Elizabeth Lyden, Douglas Stoller, Marshall Hyden, Adam Burdorf, Ronald Zolty, John Um, Brian Lowes

The VAD Journal

Background: Left ventricular assist devices (LVAD) are an increasingly used therapy for patients with advanced heart failure. Arrhythmias are common complications following LVAD implantation requiring admission, initiation, and escalation of medical therapy. Despite their frequent use in the treatment of arrhythmias, little has been reported regarding electrocardiographic changes, antiarrhythmic utilization, and outcomes post-LVAD.

Methods: A total of 309 patients who received a LVAD underwent retrospective chart review pre- and post-LVAD. Kaplan-Meier curves were calculated and compared using the log-rank test. Cox regression model was used for univariate analysis and those with a p

Results: There was a significant reduction in …

A Rare Case Of Spontaneous Cardiac Tamponade Induced By Concomitant Use Of Rivaroxaban And Amiodarone., Oreoluwa Oladiran, Jared Segal, Ifeanyi Nwosu, Salik Nazir

Reading Hospital Internal Medicine Residency

Rivaroxaban is a direct oral anticoagulant (DOAC) approved as an important alternative to warfarin in patients with nonvalvular atrial fibrillation. We report the case of an 87-year-old man with past medical history of nonvalvular atrial fibrillation on rivaroxaban and recently started amiodarone for pulseless ventricular tachycardia who presented to our hospital with intermittent chest pain and was diagnosed with spontaneous hemopericardium causing cardiac tamponade. The culprit drugs were discontinued, and the patient was treated with emergent pericardiocentesis. Both rivaroxaban and amiodarone are substrates for the CYP3A4 hepatic pathway, and concomitant use can result in increased plasma rivaroxaban levels causing an …

Left Ventricular Pseudoaneurysm: An Overview Of Diagnosis And Management., Faisal Inayat, Ali Raza Ghani, Iqra Riaz, Nouman Safdar Ali, Usman Sarwar, Raphael Bonita, Hafeez Ul Hassan Virk

Abington Jefferson Health Papers

Left ventricular pseudoaneurysm is a rare but life-threatening disorder that is frequently reported secondary to myocardial infarction or cardiac surgery. In this article, we chronicle the case of a patient with no prior risk factors who presented with a 2-week history of nonexertional atypical left chest pain. Apical 2-chamber transthoracic echocardiography revealed an unexpected outpouching of basal inferoseptal wall of the left ventricle, which had a narrow neck and relatively wide apex. The patient was diagnosed with left ventricular pseudoaneurysm and medical therapy was initiated. He refused to undergo the surgical intervention and subsequently, he was discharged from the hospital …

Safety And Efficacy Of Routine Bridging Anticoagulation For Subtherapeutic Anticoagulation In Outpatients With A Left Ventricular Assist Device, David C. Shisler, Gaurang N. Vaidya, Lori Muncy, Rajakrishnan Vijayakrishnan, Mark S. Slaughter, Emma J. Birks, Dmitry Abramov

The VAD Journal

Background

Anticoagulation with vitamin K antagonists is vital to prevent pump thrombosis in patients with left ventricular assist devices (LVADs). However, the safety and efficacy of bridging anticoagulation for the routine management of subtherapeutic international normalized ratio (INR) in stable outpatients remains poorly characterized.

Methods

In this retrospective study, a total of 60 LVAD outpatients had 110 episodes of subtherapeutic INR noted on routine testing. 34 of these episodes were managed with parenteral bridging anticoagulation and 76 were managed with only an adjusted dose of warfarin. The rates of bleeding and thromboembolic adverse events following these episodes of subtherapeutic INR …

Anti-Hypertensive Medication Use, Soluble Receptor For Glycation End Products And Risk Of Pancreatic Cancer In The Women's Health Initiative Study, Zhensheng Wang, Donna L. White, Ron Hoogeveen, Liang Chen, Eric A. Whitsel, Peter A. Richardson, Salim S. Virani, Jose M. Garcia, Hashem B. El-Serag, Li Jiao

Office of the Provost

Pancreatic cancer is the fourth leading cause of cancer death. Soluble receptor for glycation end products (sRAGE), which is modulated by anti-hypertensive (HT) medications, has been inversely associated with pancreatic cancer. However, the association between commonly used anti-HT medications and risk of pancreatic cancer is unknown. A total of 145,551 postmenopausal women from the Women Health Initiative (WHI) Study were included in analysis. Use of angiotensin converting enzyme inhibitors (ACEi), β-blockers, calcium channel blockers (CCBs) and diuretics was ascertained at baseline (1993⁻1998). Baseline sRAGE levels were measured among a subset of 2104 participants using an immunoassay. Multivariable Cox proportional hazard …

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

A Case Of Mislabeled Textbooks: Misnomer Of The Traditional "Bicaval" View., Laura Vaskelyte, Stefan Bertog, Ilona Hofmann, Bojan Jovanović, Markus Reinartz, Predrag Matić, Sameer Gafoor, Kolja Sievert, Horst Sievert

Articles, Abstracts, and Reports

Since the early beginning of the transesophageal echocardiography (TEE) era, standardized tomographic views describing cardiac key structures have been provided. They have become the basis of TEE and have not been modified for decades. During our recent structural interventional cases, it has come to our attention that the structure frequently labeled "inferior vena cava" in textbooks and journal articles illustrating the bicaval TEE view is, in fact, the coronary sinus. Our manuscript illustrates our observation.

Physician Burnout: Causes, Consequences, And (?) Cures, Herbert L Fred, Mark S Scheid

The Texas Heart Institute Journal

No abstract provided.

Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski

Department of Emergency Medicine Faculty Papers

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.

Progress Of In-Stent Restenosis After Vertebral Artery Ostium Stenosis And Imaging Assessments, Jingzhi Li, Md, John R. Eisenbrey, Phd, Yang Hua, Md

Department of Radiology Faculty Papers

Stenting has become one of the primary procedure to treat vertebral artery ostium stenosis patients. Postoperative in­stent restenosis (ISR) of the stenting is still one of the unsolved issues and requires systematic and further investigation. Through imaging assessments, ISR could be identified and evaluated in clinical practice and researches.

Sex-Related Differences In Outcomes Of Thoracic Organ Transplantation And Mechanical Circulatory Support, Daoud Daoud, Faisal H Cheema, Jeffrey A Morgan, Gabriel Loor

The Texas Heart Institute Journal

No abstract provided.

Prognostic Performance Of Prospective Versus Retrospective Electrocardiographic Gating In Coronary Computed Tomographic Angiography, Pradnya Velankar, Kongkiat Chaikriangkrai, Ninad Dewal, Sayf Khaleel Bala, Belqis Elferjani, Sama Alchalabi, Su Min Chang

The Texas Heart Institute Journal

Coronary computed tomographic angiography (CCTA) with prospective electrocardiographic gating reduces radiation exposure, but its prognostic power for predicting cardiovascular risk in patients with suspected CAD has not been fully validated. To determine whether prospective gating performs as well as retrospective gating in this population, we compared these scan modes in patients undergoing 64-slice CCTA.

From January 2009 through September 2011, 1,407 patients underwent CCTA; of these, 915 (mean age, 57.8 ± 13.5 yr; 54% male) had suspected coronary artery disease at the time of CCTA and were included in the study. Prospective gating was used in 195 (21%) and retrospective …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …