74 results on '"Hammel JM"'
Search Results
2. Trauma team activation criteria as predictors of patient disposition from the emergency department.
- Author
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Kohn MA, Hammel JM, Bretz SW, and Stangby A
- Published
- 2004
3. Stakeholders' Experiences Using Videoconferencing for a Group-Based Stroke Intervention During COVID-19: A Thematic Analysis.
- Author
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Kringle EA, Skidmore ER, Baum MC, Shih M, Rogers C, and Hammel JM
- Subjects
- United States, Adult, Humans, Learning, Videoconferencing, COVID-19, Cognitive Behavioral Therapy, Stroke
- Abstract
Importance: Guidance is limited for training protocols that support stakeholders who are new to participating in telerehabilitation interventions using videoconferencing software., Objective: To explore stakeholders' experiences participating in a group-based intervention during the coronavirus disease 2019 (COVID-19) pandemic using a videoconferencing software (Zoom)., Design: Ad hoc exploratory thematic analysis., Setting: Community-based telerehabilitation., Participants: Stakeholders included group members (n = 8) who were low-income adults with chronic stroke (≥3 mo) and mild to moderate disability (National Institutes of Health Stroke Scale ≤ 16), group leaders (n = 4), and study staff (n = 4)., Intervention: Group-based intervention, ENGAGE, delivered using videoconferencing technology. ENGAGE blends social learning and guided discovery to facilitate community and social participation., Outcomes and Measures: Semistructured interviews., Results: Stakeholders included group members (ages 26-81 yr), group leaders (ages 32-71 yr), and study staff (ages 23-55 yr). Group members characterized ENGAGE as learning, doing, and connecting with others who shared their experience. Stakeholders identified social advantages and disadvantages to the videoconferencing environment. Attitudes toward technology, past technology experiences, the amount of time allotted for training, group size, physical environments, navigation of technology disruptions, and design of the intervention workbook were facilitators for some and barriers for others. Social support facilitated technology access and intervention engagement. Stakeholders recommended training structure and content., Conclusions and Relevance: Tailored training protocols may support stakeholders who are participating in telerehabilitation interventions using new software or devices. Future studies that identify specific tailoring variables will advance the development of telerehabilitation training protocols. What This Article Adds: These findings provide stakeholder-identified barriers and facilitators, in addition to stakeholder-informed recommendations, for technology training protocols that may support uptake of telerehabilitation in occupational therapy., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
4. Norwood Operation: Immediate vs Delayed Sternal Closure.
- Author
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Asfari A, Jacobs JP, Byrnes JW, Borasino S, Prodhan P, Zaccagni H, Dabal RJ, Sorabella RA, Hammel JM, Smith-Parrish M, Zhang W, Banerjee M, Schumacher KR, and Tabbutt S
- Subjects
- Infant, Newborn, Humans, Child, Retrospective Studies, Sternum surgery, Postoperative Complications etiology, Surgical Wound Infection epidemiology, Cardiac Surgical Procedures adverse effects, Norwood Procedures adverse effects
- Abstract
Background: The Norwood operation is a complex neonatal surgery. There are limited data to inform the timing of sternal closure. After the Norwood operation, delayed sternal closure (DSC) is frequent. We aimed to examine the association of DSC with outcomes, with a particular interest in how sternal closure at the time of surgery compared with the timing of DSC. Our outcomes included mortality, length of ventilation, length of stay, and postoperative complications., Methods: This retrospective study included neonates who underwent a Norwood operation reported in the Pediatric Cardiac Critical Care Consortium registry from February 2019 through April 2021. Outcomes of patients with closed sternum were compared to those with sternal closure prior to postoperative day 3 (early closure) and prior to postoperative day 6 (intermediate closure)., Results: The incidence of DSC was 74% (500 of 674). The median duration of open sternum was 4 days (interquartile range 3-5 days). Comparing patients with closed sternum to patients with early sternal closure, there was no statistical difference in mortality rate (1.1% vs 0%) and the median hospital postoperative stay (30 days vs 31 days). Compared with closed sternum, patients with intermediate sternal closure required longer mechanical ventilation (5.9 days vs 3.9 days) and fewer subsequent sternotomies (3% vs 7.5%)., Conclusions: For important outcomes following the Norwood operation there is no advantage to chest closure at the time of surgery if the chest can be closed prior to postoperative day 3., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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5. Discussion.
- Author
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Hammel JM
- Published
- 2022
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6. The American Association for Thoracic Surgery Congenital Cardiac Surgery Working Group 2021 consensus document on a comprehensive perioperative approach to enhanced recovery after pediatric cardiac surgery.
- Author
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Fuller S, Kumar SR, Roy N, Mahle WT, Romano JC, Nelson JS, Hammel JM, Imamura M, Zhang H, Fremes SE, McHugh-Grant S, and Nicolson SC
- Subjects
- Age Factors, Cardiac Surgical Procedures adverse effects, Consensus, Delphi Technique, Evidence-Based Medicine standards, Humans, Recovery of Function, Time Factors, Treatment Outcome, Cardiac Surgical Procedures standards, Cardiology standards, Enhanced Recovery After Surgery standards, Heart Defects, Congenital surgery, Pediatrics standards
- Published
- 2021
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7. The Complex Nature of Emboli Detection During Cardiac Procedures.
- Author
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Bashford GR, Truemper EJ, Twedt MH, Hage BD, Hammel JM, Ibrahimye AN, Shukry M, Qadeer A, and Eskridge KM
- Subjects
- Humans, Cardiopulmonary Bypass, Thoracic Surgical Procedures
- Published
- 2021
- Full Text
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8. Interruption of the Ascending Aorta-Biventricular Surgical Repair.
- Author
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Fletcher BS, Christensen JT, Hammel JM, and Fletcher SE
- Subjects
- Aorta, Thoracic diagnostic imaging, Brachiocephalic Trunk diagnostic imaging, Echocardiography methods, Female, Humans, Infant, Vascular Malformations diagnosis, Aorta, Thoracic surgery, Brachiocephalic Trunk surgery, Cardiac Surgical Procedures methods, Vascular Malformations surgery
- Abstract
Interruption of the ascending aorta is an extremely rare anomaly defined by a point of interruption between the intrapericardial and extrapericardial aorta and can be explained by developmental errors proximal to the embryologic right aortic sac. Herein, we present a case of interruption of the ascending aorta and describe a successful biventricular surgical repair of this unique anomaly.
- Published
- 2021
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9. Williams Syndrome and Neonatal Cardiac Surgery for Congenital Single Ventricle.
- Author
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Katt TE, Spicer RL, Yetman AT, Ibrahimiye AN, Hammel JM, and Robinson JA
- Abstract
Williams syndrome (WS) is an arteriopathic derangement associated with supravalvular aortic stenosis and branch pulmonary stenosis. We describe double-outlet right ventricle with mitral atresia and aortic arch hypoplasia in an infant with WS. This case demonstrates the difficulty in managing patients with WS with complex cardiac defects. To our knowledge, this is the first reported single-ventricle physiology in a patient with WS. ( Level of Difficulty: Advanced. )., (© 2020 The Authors.)
- Published
- 2020
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10. Most High-Intensity Transient Signals Are Not Associated With Specific Surgical Maneuvers.
- Author
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Twedt MH, Hage BD, Hammel JM, Ibrahimye AN, Shukry M, Qadeer A, Eskridge KM, Truemper EJ, and Bashford GR
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- Child, Preschool, Female, Humans, Infant, Infant, Newborn, Intracranial Embolism etiology, Intracranial Embolism physiopathology, Male, Heart Defects, Congenital surgery, Intracranial Embolism diagnosis, Ultrasonography, Doppler, Transcranial methods
- Abstract
Background: Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children., Methods: Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS)., Results: An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers., Conclusions: In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.
- Published
- 2020
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11. Infundibular sparing versus transinfundibular approach to the repair of tetralogy of Fallot.
- Author
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Olive MK, Fraser CD, Kutty S, McKenzie ED, Hammel JM, Krishnamurthy R, Dodd NA, and Maskatia SA
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Magnetic Resonance Imaging, Cine, Male, Nebraska, Recovery of Function, Retrospective Studies, Risk Factors, Stroke Volume, Tetralogy of Fallot diagnostic imaging, Tetralogy of Fallot physiopathology, Texas, Treatment Outcome, Ventricular Function, Left, Ventricular Function, Right, Cardiac Surgical Procedures adverse effects, Tetralogy of Fallot surgery
- Abstract
Introduction: The right ventricular infundibular sparing approach (RVIS) to the repair of tetralogy of Fallot (TOF) avoids a full-thickness ventricular incision, typically utilized in the transinfundibular (TI) method., Methods: We performed a retrospective, age-matched cohort study of patients who underwent RVIS at Texas Children's Hospital or TI at Children's Hospital Medical Center in Nebraska and subsequently underwent cardiac magnetic resonance imaging (CMR). We compared right ventricular end-diastolic and systolic volumes indexed to body surface area (RVEDVi and RVESVi) and right ventricular ejection fraction (RVEF) as primary endpoints. Secondary endpoints were indexed left ventricular diastolic and systolic volume (LVEDVi and LVESVi), left ventricular ejection fraction (LVEF), right ventricular (RV) sinus ejection fraction (EF) and RV outflow tract EF (RVOT EF)., Results: Seventy-nine patients were included in the analysis; 40 underwent RVIS and 39 underwent TI repair. None of the patients in the TI repair group had an initial palliation with a systemic to pulmonary arterial shunt compared to seven (18%) in the RVIS group (P < .01). There was no appreciable difference in RVEDVi (122 ± 29 cc/m
2 vs 130 ± 29 cc/m2 , P = .59) or pulmonary regurgitant fraction (40 ± 13 vs 37 ± 18, P = .29) between the RVIS and TI groups. Compared to the TI group, the RVIS group had higher RVEF (54 ± 6% vs 44 ± 9%, P < .01), lower RVESV (57 ± 17 cc/m2 vs 67 ± 25 cc/m2 , P = .03), higher LVEF (61 ± 11% vs 54 ± 8%, P < .01), higher RVOT EF (47 ± 12% vs 41 ± 11%, P = .03), and higher RV sinus EF (56 ± 5% vs 49 ± 6%, P < .01) CONCLUSIONS: In this selected cohort, patients who underwent RVIS repair for TOF had higher right and left ventricular ejection fraction compared to those who underwent TI repair., (© 2020 Wiley Periodicals, Inc.)- Published
- 2019
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12. Commentary: First survive the crash: When to bail on the unbalanced atrioventricular valve.
- Author
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Hammel JM
- Subjects
- Humans, Infant, Cardiac Surgical Procedures, Heart Septal Defects, Univentricular Heart
- Published
- 2019
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13. Outcomes related to immediate extubation after stage 1 Norwood palliation for hypoplastic left heart syndrome.
- Author
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Varghese J, Hammel JM, Ibrahimiye AN, Siecke R, Bisselou Moukagna KS, and Kutty S
- Subjects
- Female, Hospital Mortality, Humans, Hypoplastic Left Heart Syndrome diagnosis, Hypoplastic Left Heart Syndrome mortality, Hypoplastic Left Heart Syndrome physiopathology, Infant, Newborn, Intubation, Intratracheal, Male, Postoperative Complications mortality, Postoperative Complications therapy, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Airway Extubation adverse effects, Airway Extubation mortality, Hypoplastic Left Heart Syndrome surgery, Norwood Procedures adverse effects, Norwood Procedures mortality, Palliative Care, Time-to-Treatment
- Abstract
Objective: Immediate extubation may have outcome benefits when judiciously instituted after neonatal congenital cardiac surgery. We sought to evaluate the outcomes of immediate extubation specifically in neonates undergoing stage 1 Norwood palliation of hypoplastic left heart syndrome., Methods: Consecutive neonates undergoing stage 1 Norwood (January 2010 to December 2016) for hypoplastic left heart syndrome were retrospectively studied. Immediate extubation was defined as successful extubation before termination of anesthetic care. Preoperative and intraoperative variables were compared between immediate extubation and nonimmediate extubation groups, and bivariate analyses and descriptive methods were used to express the association of outcome variables with immediate extubation. Data were expressed as number and percent for categoric variables, and median and interquartile range for continuous variables., Results: Of 23 patients who underwent stage 1 palliation, 5 had immediate extubation (22%). There were no differences in preoperative or intraoperative factors between patients who did and did not undergo immediate extubation. There were no deaths in the immediate extubation group. In the nonimmediate extubation group, 3 patients died before hospital discharge. One patient who had immediate extubation and 4 patients among those who did not have immediate extubation had to be reintubated in the 96 hours that followed extubation (P = 1). Intensive care unit length of stay was 8 (3-17) and 8 (5-18) (days) for the immediate extubation group and nonimmediate extubation groups, respectively (P = .71)., Conclusions: Immediate extubation strategy was safely accomplished in one-fifth of this cohort of hypoplastic left heart syndrome. A larger cohort may delineate the determinants of immediate extubation and its benefits in infants undergoing stage 1 single ventricle palliation., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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14. Evaluation of cellular ingrowth within porcine extracellular matrix scaffolding in congenital heart disease surgery.
- Author
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Cox JL, Hammel JM, and Radio SJ
- Subjects
- Animals, Autopsy, Biopsy, Child, Preschool, Collagen metabolism, Extracellular Matrix metabolism, Extracellular Matrix pathology, Female, Glycosaminoglycans metabolism, Heart Defects, Congenital metabolism, Heart Defects, Congenital pathology, Heterografts, Humans, Infant, Intestine, Small metabolism, Intestine, Small pathology, Male, Surface Properties, Sus scrofa, Time Factors, Treatment Outcome, Cardiac Surgical Procedures, Cell Proliferation, Extracellular Matrix transplantation, Heart Defects, Congenital surgery, Intestine, Small transplantation
- Abstract
The search for an ideal material for cardiac tissue repair has led to utilization of porcine small intestinal submucosa extracellular matrix (CorMatrix). Here, we examine the histologic features of CorMatrix and the associated cellular growth at a variety of time intervals. Tissues with CorMatrix from ten patients (4 male, 6 female) with ages ranging from 2 weeks to 2 years, and implant duration ranging from 1 week to 2 years were included in this study. Samples for analysis were collected at autopsy. Surgical repair sites included great vessel repair (n=9), atrial septum defect (n=1), coronary vessels (n=1), as well as aortic (n=1) and mitral valve (n=2) leaflets. In all specimens, CorMatrix was composed of dense laminated regions of collagen, without appreciable elastin staining. In most grafts, especially those implanted for extended periods of time, tissue with luminal CD31 positivity covered the intimal surface of the CorMatrix graft. This tissue (neo-intima) consisted of spindled myofibroblasts (SMA) and small CD31 positive vessels with occasional mononuclear cells in a matrix composed of collagen, glycosaminoglycans, and rarely elastin, after extended periods of implantation. These features were readily identified in patients as early as 1 month after CorMatrix implantation. The matrix comprising the CorMatrix itself remained largely acellular, despite implantation times up to 2 years, with degradation of the graft material. We provide a framework for histologic expectations when evaluating explanted CorMatrix grafts. In this regard, the CorMatrix matrix is likely to remain acellular without significant elastin deposition, whereas the intimal and adventitial surfaces become coated by proliferating cells in a novel matrix of collagen and glycosaminoglycans., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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15. Dental Emergencies.
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Hammel JM and Fischel J
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- Emergencies, Focal Infection, Dental diagnosis, Focal Infection, Dental therapy, Humans, Mouth injuries, Oral Hemorrhage etiology, Pain etiology, Stomatognathic Diseases pathology, Stomatognathic Diseases therapy, Tooth Avulsion diagnosis, Tooth Avulsion therapy, Tooth Injuries diagnosis, Tooth Injuries therapy, Stomatognathic Diseases diagnosis
- Abstract
Dental emergencies present frequently to the emergency department and urgent care centers. Trauma to the teeth includes fractures, luxations, and avulsions, which can be reduced in most cases. Avulsed primary teeth should never be replaced. Mouthguards should be worn in most youth sports to prevent many dental injuries. Dental caries can progress to worsening infection and should be diagnosed and promptly referred. More severe infections may require antibiotics, imaging, or incision and drainage. Dental blocks can assist with analgesia and patient comfort during other procedures., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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16. Invited Commentary.
- Author
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Hammel JM
- Subjects
- Hospitals, Humans, United States, Cardiac Surgical Procedures
- Published
- 2019
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17. What's Sauce for the Goose…; Why Not Treat Normal Organs as Well as Injured Ones?
- Author
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Hammel JM
- Subjects
- Animals, Catheterization, Ductus Arteriosus, Geese, Aorta, Thoracic, Aortic Diseases
- Published
- 2019
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18. Supplemental Perfusion Techniques for Aortic Arch Reconstruction, With Emphasis on Direct Cannulation of the Descending Aorta.
- Author
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Hammel JM
- Subjects
- Humans, Infant, Newborn, Aorta, Thoracic surgery, Brachiocephalic Trunk surgery, Cardiopulmonary Bypass methods, Catheterization methods, Heart Defects, Congenital surgery, Hypothermia, Induced methods
- Abstract
The established techniques of deep hypothermia with circulatory arrest and regional cerebral perfusion expose infants and children to additional physiologic stress and deleterious effects which may adversely affect the outcome of operations involving reconstruction of the aortic arch. Alternative techniques to supplement perfusion support are an area of innovation today. The most effective adjunct for somatic perfusion during arch reconstruction is direct cannulation of the innominate artery and the descending aorta, with full flow at mild hypothermia distributed throughout the entire body just as it is during routine, single cannulation surgery with an intact aorta. Detailed facilitating techniques for descending aortic cannulation are discussed., (Copyright © 2019 The Author. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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19. Surgical Atrioventricular Valve Replacement With Melody Valve in Infants and Children.
- Author
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Pluchinotta FR, Piekarski BL, Milani V, Kretschmar O, Burch PT, Hakami L, Meyer DB, Jacques F, Ghez O, Trezzi M, Carotti A, Qureshi SA, Michel-Behnke I, Hammel JM, Chai P, McMullan D, Mettler B, Ferrer Q, Carminati M, and Emani SM
- Subjects
- Adolescent, Age Factors, Child, Child, Preschool, Echocardiography, Doppler, Color, Europe, Female, Heart Valve Prosthesis Implantation adverse effects, Heart Valve Prosthesis Implantation mortality, Hemodynamics, Humans, Infant, Infant, Newborn, Male, Mitral Valve diagnostic imaging, Mitral Valve physiopathology, Mitral Valve Prolapse diagnostic imaging, Mitral Valve Prolapse mortality, Mitral Valve Prolapse physiopathology, Mitral Valve Stenosis diagnostic imaging, Mitral Valve Stenosis mortality, Mitral Valve Stenosis physiopathology, North America, Postoperative Complications physiopathology, Postoperative Complications therapy, Prosthesis Design, Recovery of Function, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Bioprosthesis, Heart Valve Prosthesis, Heart Valve Prosthesis Implantation instrumentation, Mitral Valve surgery, Mitral Valve Prolapse surgery, Mitral Valve Stenosis surgery
- Abstract
Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes <15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P<0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.
- Published
- 2018
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20. Eliciting Narratives to Inform Care for Infants With Trisomy 18.
- Author
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Weaver MS, Starr LJ, Austin PN, Stevenson CL, and Hammel JM
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- Female, Humans, Infant, Patient Care psychology, Pregnancy, Trisomy 18 Syndrome psychology, Narration, Patient Care ethics, Trisomy 18 Syndrome diagnosis, Trisomy 18 Syndrome surgery
- Abstract
: media-1vid110.1542/5804913218001PEDS-VA_2018-0321 Video Abstract ., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)
- Published
- 2018
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21. Right ventricular energetics and power in pulmonary regurgitation vs. stenosis using four dimensional phase contrast magnetic resonance.
- Author
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Fernandes JF, Hammel JM, Zhou J, Xiao Y, Chen M, Alves R, Lof J, Grieve SM, Schuster A, Kuehne T, and Kutty S
- Subjects
- Animals, Contrast Media, Echocardiography methods, Swine, Magnetic Resonance Imaging, Cine methods, Pulmonary Valve Insufficiency diagnostic imaging, Pulmonary Valve Insufficiency physiopathology, Pulmonary Valve Stenosis diagnostic imaging, Pulmonary Valve Stenosis physiopathology, Ventricular Function, Right physiology
- Abstract
Objective: We investigated a full energetic profile of pressure and volume loaded right ventricle (RV) in porcine models by evaluating kinetic energy (KE), stroke power, power output and power loss across pulmonary valves with stenosis (PS) or with regurgitation (PR)., Methods: Fifteen pigs (6 PS and 6 PR, 3 unoperated controls) were studied. Phase-contrast 4D-flow MRI was performed in models of PS and PR at baseline and at 10-12 weeks, in conjunction with cardiac catheterization. Phase contrast velocities over 1 cardiac cycle were registered with a dynamic mask of the RV segmented from cine images. Mean KE and KE curve profiles were measured, normalized for RV volumes and compared between groups. Right heart catheterization pressures were used to calculate RV stroke power and power output, from which pulmonary valve power loss and RV power output ratio were calculated, and compared between groups., Results: PS and PR groups had similar KE pre procedure but significant changes in KE post procedure. The PR group had higher RV power output ratio and KE (72.1% ± 11.4%; 20.6 ± 6.1) than PS group (25.6% ± 4.7%; 13.8 ± 5.0) post procedure. Volume loaded RV from PR had higher KE and power output ratio compared to pressure load from PS., Conclusions: In porcine models of PS and PR, the RV presents altered systolic and diastolic energetic profiles. Pulmonary valve efficiency appeared to decrease in the medium term with somatic growth, with increased power loss in all groups studied, and greatly within the PS group., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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22. Assembling the puzzle of polymorphism.
- Author
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Hammel JM
- Subjects
- Humans, Infant, Cardiac Surgical Procedures, Mannose-Binding Lectin deficiency, Metabolism, Inborn Errors
- Published
- 2018
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23. Catheter palliation or early surgery for tetralogy of Fallot: Options when timing is less than ideal.
- Author
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Hammel JM
- Subjects
- Cardiovascular System growth & development, Disease Progression, Health Status, Humans, Patient Selection, Reproducibility of Results, Cardiac Catheterization methods, Cardiac Surgical Procedures methods, Early Medical Intervention methods, Palliative Care methods, Tetralogy of Fallot surgery
- Published
- 2017
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24. Peace at the interface of human and machine.
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Hammel JM
- Subjects
- Child, Hemostasis, Humans, Anticoagulants, Heart-Assist Devices
- Published
- 2017
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25. Mitochondrial autotransplantation: A "shot" in the dark?
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Hammel JM
- Subjects
- Humans, Transplantation, Autologous, Reperfusion Injury
- Published
- 2017
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26. The lonely ventricle in chronic Fontan circulation.
- Author
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Hammel JM
- Subjects
- Heart Ventricles surgery, Fontan Procedure
- Published
- 2017
- Full Text
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27. Five-year experience with immediate extubation after arterial switch operations for transposition of great arteries.
- Author
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Varghese J, Kutty S, Bisselou Moukagna KS, Craft M, Abdullah I, and Hammel JM
- Subjects
- Anesthesia, General methods, Critical Care, Heart Septal Defects, Ventricular pathology, Humans, Infant, Newborn, Length of Stay statistics & numerical data, Postoperative Care methods, Postoperative Period, Retrospective Studies, Transposition of Great Vessels pathology, Treatment Outcome, Airway Extubation methods, Arterial Switch Operation methods, Transposition of Great Vessels surgery
- Abstract
Objectives: We sought to identify preoperative, intraoperative and anatomical factors associated with immediate extubation (IE) after arterial switch operation for d-transposition of great arteries (dTGA)., Methods: This was a single-centre retrospective study performed from 1 January 2010 to 30 June 2015. IE was defined as successful extubation in the operating room (OR). Univariate/bivariate regression of preoperative, intraoperative and anatomical variables was used to determine associations with IE., Results: Of 32 patients in the dTGA spectrum (age at operation 6 days), 18 (56%) underwent IE. Twelve (71%) of the 17 patients with an intact ventricular septum and 6 (43%) of the 14 patients with ventricular septal defect (VSD) underwent IE, whereas none of the patients with double outlet right ventricle or aortic arch obstruction ( n = 4) did. Patients who had cardiopulmonary bypass time (CPB) >173 min ( P = 0.01), lowest temperature on CPB (T min) ≤ 30.4°C ( P = 0.04) and aortic cross-clamp time >86 min ( P = 0.04) were more likely to be left intubated at the end of the procedure. There was no significant difference in patient's chronological age, gestational age, post-conceptual age, weight, coronary anatomy or prevalence of VSD between those who did and did not undergo IE. There was a median increase in intensive care unit (ICU) length of stay (LOS) by 1 day (33%, P = 0.03) and ICU costs by $12 338 (15%, P = 0.06) in non-IE patients. The OR turnover time ( P = 0.09) and reintubation rate ( P = 1) at 24 h post-extubation did not differ between those who did and did not have IE. There was no myocardial dysfunction evident on predismissal echocardiography in either group., Conclusions: In this cohort of infants, post repair for TGA, 56% were extubated immediately in the OR. Greater CPB and cross-clamp times and T min ≤ 30.4°C were associated with a lesser likelihood of IE. IE was associated with shorter ICU length of stay., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
- Published
- 2017
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28. Preoperative and Intraoperative Predictive Factors of Immediate Extubation After Neonatal Cardiac Surgery.
- Author
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Varghese J, Kutty S, Abdullah I, Hall S, Shostrom V, and Hammel JM
- Subjects
- Anesthesia economics, Anesthesia methods, Anesthesia statistics & numerical data, Cardiopulmonary Bypass, Female, Gestational Age, Hospital Costs, Humans, Infant, Newborn, Intensive Care Units, Pediatric economics, Intensive Care Units, Pediatric statistics & numerical data, Intubation, Intratracheal economics, Intubation, Intratracheal statistics & numerical data, Length of Stay economics, Length of Stay statistics & numerical data, Male, Operating Rooms economics, Operative Time, Postoperative Care economics, Postoperative Complications epidemiology, Postoperative Complications therapy, ROC Curve, Recovery Room economics, Recovery Room statistics & numerical data, Reoperation statistics & numerical data, Respiration, Artificial statistics & numerical data, Retrospective Studies, Airway Extubation economics, Airway Extubation statistics & numerical data, Cardiac Surgical Procedures economics, Postoperative Care statistics & numerical data
- Abstract
Background: We sought to identify preoperative and intraoperative predictors of immediate extubation (IE) after open heart surgery in neonates. The effect of IE on the postoperative intensive care unit (ICU) length of stay (LOS), cost of postoperative ICU care, operating room turnover, and reintubation rates was assessed., Methods: Patients younger than 31 days who underwent cardiac surgery with cardiopulmonary bypass (January 2010 to December 2013) at a tertiary-care children's hospital were studied. Immediate extubation was defined as successful extubation before termination of anesthetic care. Data on preoperative and intraoperative variables were compared using descriptive, bivariate, and multivariate statistics to identify the predictors of IE. Propensity scores were used to assess effects of IE on ICU LOS, the cost of ICU care, reintubation rates, and operating room turnover time., Results: One hundred forty-eight procedures done at a median age of 7 days resulted in 45 IEs (30.4%). The IE rate was 22.2% with single-ventricle heart disease. Independent predictors of IE were the absence of the need for preoperative ventilatory assistance, higher gestational age, anesthesiologist, and shorter cardiopulmonary bypass. Immediate extubation was associated with shorter ICU LOS (8.3 versus 12.7 days; p < 0.0001) and lower cost of ICU care (mean postoperative ICU charges, $157,449 versus $198,197; p < 0.0001) with no significant difference in the probability of reintubation (p = 0.7). Immediate extubation was associated with longer operating room turnover time (38.4 versus 46.7 minutes; p = 0.009)., Conclusions: Immediate extubation was accomplished in 30.4% of neonates undergoing open heart surgery involving cardiopulmonary bypass. Immediate extubation was associated with lesser ICU LOS, postoperative ICU costs, and minimal increase in operating room turnover time, but without an increase in reintubation rates. Low gestational age, preoperative ventilatory support requirement, and prolonged cardiopulmonary bypass time were inversely associated with the ability to accomplish IE., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2016
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29. Myhre syndrome: Clinical features and restrictive cardiopulmonary complications.
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Starr LJ, Grange DK, Delaney JW, Yetman AT, Hammel JM, Sanmann JN, Perry DA, Schaefer GB, and Olney AH
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- Child, Cryptorchidism complications, Electrocardiography, Facies, Female, Growth Disorders complications, Hand Deformities, Congenital complications, Heart Transplantation, Humans, Intellectual Disability complications, Male, Mutation, Pregnancy, Smad4 Protein genetics, Young Adult, Cryptorchidism etiology, Cryptorchidism therapy, Growth Disorders etiology, Growth Disorders therapy, Hand Deformities, Congenital etiology, Hand Deformities, Congenital therapy, Heart Diseases surgery, Intellectual Disability etiology, Intellectual Disability therapy
- Abstract
Myhre syndrome, a connective tissue disorder characterized by deafness, restricted joint movement, compact body habitus, and distinctive craniofacial and skeletal features, is caused by heterozygous mutations in SMAD4. Cardiac manifestations reported to date have included patent ductus arteriosus, septal defects, aortic coarctation and pericarditis. We present five previously unreported patients with Myhre syndrome. Despite varied clinical phenotypes all had significant cardiac and/or pulmonary pathology and abnormal wound healing. Included herein is the first report of cardiac transplantation in patients with Myhre syndrome. A progressive and markedly abnormal fibroproliferative response to surgical intervention is a newly delineated complication that occurred in all patients and contributes to our understanding of the natural history of this disorder. We recommend routine cardiopulmonary surveillance for patients with Myhre syndrome. Surgical intervention should be approached with extreme caution and with as little invasion as possible as the propensity to develop fibrosis/scar tissue is dramatic and can cause significant morbidity and mortality., (© 2015 Wiley Periodicals, Inc.)
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- 2015
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30. Predischarge Transthoracic Echocardiography after Surgery for Congenital Heart Disease: A Routine with a Reason?
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Shoiab I, Danford DA, Li L, Abdullah I, Hammel JM, and Kutty S
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- Adolescent, Adult, Child, Child, Preschool, Female, Follow-Up Studies, Heart Defects, Congenital surgery, Humans, Infant, Infant, Newborn, Male, Postoperative Period, Reproducibility of Results, Retrospective Studies, Time Factors, Young Adult, Cardiac Surgical Procedures, Echocardiography methods, Heart Defects, Congenital diagnostic imaging, Patient Discharge
- Abstract
Background: Predischarge (pre-d/c) transthoracic echocardiography (TTE) is routine after surgery for congenital heart disease, but how it affects clinical care is unknown. The aim of this study was to test the hypothesis that pre-d/c TTE frequently reveals findings associated with short-term clinical course through a systematic review of findings on pre-d/c TTE and clinical events that followed., Methods: Clinical outcomes of mortality, hospitalization, catheterization, and surgery at 1 year were examined for pediatric patients undergoing pre-d/c TTE between June 2010 and June 2012. Using logistic regression, a multivariate model was generated associating clinical, pre-d/c transthoracic echocardiographic, and demographic variables with unplanned postdischarge cardiac events (UCEs) within 1 year., Results: Of 462 patients who underwent pre-d/c TTE, there were 265 male patients (57%) and 197 female patients (43%); the median age was 0.8 years (range, 0-33 years). Two hundred thirty-seven patients (51%) had findings (valve regurgitation, hemodynamic obstruction, ventricular dysfunction, unintended shunt, or pericardial effusion) on pre-d/c TTE, 57 of which were of more than mild severity. Agreement between pre-d/c TTE and postoperative transesophageal echocardiographic findings was only fair to moderate (κ = 0.27-0.43). Sixty-four patients (14%) had UCEs. Univariate analysis revealed that UCE were more frequent in patients with diagnoses and surgical procedures of high complexity. After accounting for these confounding nonechocardiographic variables, pre-d/c transthoracic echocardiographic findings, specifically valve regurgitation of more than mild severity, and ventricular dysfunction and obstructions of any severity were independently associated with UCEs (odds ratios, 1.90, 1.99, and 1.85, respectively)., Conclusions: Findings on pre-d/c TTE are frequent, commonly discordant with postoperative transesophageal echocardiographic results, and associated with adverse clinical events after surgery for congenital heart disease. These data would strongly support the practice of pre-d/c TTE after surgery for congenital heart disease., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)
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- 2015
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31. Fetal and neonatal imaging and strategy of primary neonatal heart transplantation in hypoplastic left heart with Ebstein's anomaly.
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Hammel JM, Danford DA, Spicer RL, and Kutty S
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- Echocardiography methods, Female, Humans, Infant, Newborn, Neonatal Screening methods, Pregnancy, Surgery, Computer-Assisted methods, Treatment Outcome, Young Adult, Ebstein Anomaly diagnostic imaging, Ebstein Anomaly surgery, Heart Transplantation, Hypoplastic Left Heart Syndrome diagnostic imaging, Hypoplastic Left Heart Syndrome surgery, Ultrasonography, Prenatal methods
- Abstract
We present the anatomic constellation of mitral stenosis/aortic atresia variant of hypoplastic left heart syndrome, Ebstein's anomaly, and partial anomalous pulmonary venous return, an exceeding rare congenital heart defect. Prenatal echocardiography led to concern about the capacity of the right ventricle to increase cardiac output with lung expansion and pulmonary arterial runoff at birth, prompting the precaution of extracorporeal membrane oxygenator standby at delivery. Stage I palliation was not attempted, and control of pulmonary arterial blood flow was achieved with pulmonary artery banding, allowing sufficient ongoing hemodynamic stability. Orthotopic cardiac transplantation, repair of hypoplastic aortic arch, and primary sutureless repair of left pulmonary veins was performed, using dual-site arterial cannulation and continuous mild hypothermic cardiopulmonary bypass. We discuss how this unique echocardiographic anatomy influenced the surgical decision and point out how it guided therapy toward a strategy of primary transplantation rather than standard staged surgical palliation., (© 2014, Wiley Periodicals, Inc.)
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- 2015
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32. Combined heart and liver transplantation against positive cross-match for patient with hypoplastic left heart syndrome.
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Raichlin E, Um JY, Duncan KF, Dumitru I, Lowes BD, Moulton M, Gebhart CL, Grant WJ, and Hammel JM
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- Adolescent, Blood Transfusion, Female, Fontan Procedure, Herpesvirus 4, Human, Histocompatibility Testing, Humans, Hypoplastic Left Heart Syndrome complications, Liver Cirrhosis complications, Liver Cirrhosis surgery, Male, Postoperative Period, Treatment Outcome, Young Adult, Heart Transplantation methods, Hypoplastic Left Heart Syndrome surgery, Liver Transplantation methods
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- 2014
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33. Staged Left Ventricular Recruitment and Biventricular Conversion in Hypoplastic Left Heart Syndrome.
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Hammel JM, House AV, Danford DA, and Kutty S
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- Echocardiography, Heart Ventricles diagnostic imaging, Humans, Hypoplastic Left Heart Syndrome diagnosis, Infant, Newborn, Male, Cardiac Surgical Procedures methods, Heart Ventricles surgery, Hypoplastic Left Heart Syndrome surgery
- Abstract
We describe a relatively long left ventricular recruitment pathway consisting of early and serial aortic valvuloplasties and multiple endocardial fibroelastosis resections resulting in successful biventricular conversion of hypoplastic left heart syndrome., (© The Author(s) 2014.)
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- 2014
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34. Transthoracic echocardiography in pediatric intensive care: impact on medical and surgical management.
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Kutty S, Attebery JE, Yeager EM, Natarajan S, Li L, Peng Q, Truemper E, Hammel JM, and Danford DA
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- Critical Illness, Female, Heart Diseases surgery, Humans, Incidental Findings, Infant, Infant, Newborn, Lung Diseases diagnostic imaging, Male, Prospective Studies, Time Factors, Echocardiography, Heart Diseases diagnostic imaging, Heart Diseases therapy, Intensive Care Units, Pediatric
- Abstract
Objectives: Although transthoracic echocardiography is commonly performed in the PICU, its utility is not specifically known. The purpose of this investigation was to evaluate the clinical impact of echocardiography in the PICU in terms of frequency of unanticipated findings and the frequency and nature of clinical management changes attributed to the results of echocardiography., Design: Prospective cohort study., Setting: Nineteen-bed combined medical-surgical-cardiac PICU at a tertiary care children's hospital., Patients: All patients in PICU undergoing transthoracic echocardiography., Interventions, Measurements, and Main Results: Data collected included echocardiography indications, pre-echocardiography clinical assessment of anticipated echocardiography findings, height, weight, primary diagnosis, age, and urgency (stat vs routine) of echocardiography. Input of the attending care team (intensivist, cardiologist, and/or cardiovascular surgeon) allowed classification of echocardiography results as either confirming the pre-echocardiography impression, altering the pre-echocardiography clinical impression regarding the indication for which the test was performed, or altering the impression by virtue of new findings unrelated to the specific indication. The nature of the new findings were recorded and categorized. The team recorded clinical management changes made in response to the echocardiography results; the nature of these were listed and categorized. Echocardiograms (n = 416) were performed in 132 patients. Of these, 244 echocardiograms (59%) were ordered on male patients, 31% were under 30 days old, median age was 103 days, 379 (91%) had a primary cardiac diagnosis, and 92 (22%) were ordered stat. Sixty-three percent of echocardiograms confirmed and 24% altered the pre-echocardiography impression regarding the indication for the echocardiography; 13% introduced new findings unrelated to the indication. Cardiac surgical revision was the management change required in 26 patients (6.3%). Stat echocardiography was more likely to alter the pre-echocardiography assessment than routine echocardiography (p < 0.001). Management changes were more commonly associated with stat echocardiograms (p = 0.002) and those with new unexpected findings (p < 0.001) but had no demonstrable association with age less than 30 days (p = 0.332)., Conclusions: Unanticipated echocardiography results are common in the PICU, and they often alter the clinical impressions that prompted the echocardiogram or introduce new findings unrelated to the reason for which the echocardiogram was recorded. Clinical management changes attributable to echocardiography findings are frequent in the PICU, including occasional surgical intervention. Echocardiography adds diagnostic value and contributes to the management approach in the PICU, accounting for its frequent use.
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- 2014
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35. Prevention of arteriovenous shunt occlusion using microbubble and ultrasound mediated thromboprophylaxis.
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Kutty S, Wu J, Hammel JM, Abraham JR, Venkataraman J, Abdullah I, Danford DA, Radio SJ, Lof J, and Porter TR
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- Animals, Arteriovenous Shunt, Surgical instrumentation, Blood Vessel Prosthesis, Blood Vessel Prosthesis Implantation instrumentation, Carotid Arteries diagnostic imaging, Carotid Arteries pathology, Disease Models, Animal, Echocardiography, Doppler, Color, Graft Occlusion, Vascular diagnostic imaging, Graft Occlusion, Vascular etiology, Graft Occlusion, Vascular pathology, Jugular Veins diagnostic imaging, Jugular Veins pathology, Polytetrafluoroethylene, Prosthesis Design, Swine, Thrombosis diagnostic imaging, Thrombosis etiology, Thrombosis pathology, Arteriovenous Shunt, Surgical adverse effects, Blood Vessel Prosthesis Implantation adverse effects, Contrast Media therapeutic use, Graft Occlusion, Vascular prevention & control, Microbubbles, Thrombosis prevention & control, Ultrasonic Therapy
- Abstract
Background: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts., Methods and Results: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt in each animal. After shunt implantation, animals were randomly assigned to one of 3 groups. Transcutaneous, weekly 30-minute treatments (total of 4 treatments) of either guided high MI US+MB (Group 1; n=6) using a 3% MRX-801 MB infusion, or US alone (Group 2; n=6) were given separately to each shunt. The third group of 6 pigs received no treatments. The shunts were explanted after 4 weeks and analyzed by histopathology to quantify luminal thrombus area (mm2) for the length of each shunt. No pigs received antiplatelet agents or anticoagulants during the treatment period. The median overall thrombus burden in the 3 groups for AV shunts was 5.10 mm2 compared with 4.05 mm(2) in AA (P=0.199). Group 1 pigs had significantly less thrombus burden in the AV shunts (median 2.5 mm2) compared with Group 2 (median 5.6 mm2) and Group 3 (median 7.5 mm2) pigs (P=0.006). No difference in thrombus burden was seen between groups for AA shunts., Conclusion: Transcutaneous US with intravenous MB is capable of preventing thrombus accumulation in arteriovenous shunts without the need for antiplatelet agents, and may be a method of preventing progressive occlusion of palliative shunts.
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- 2014
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36. Newborn aortic arch reconstruction with descending aortic cannulation improves postoperative renal function.
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Hammel JM, Deptula JJ, Karamlou T, Wedemeyer E, Abdullah I, and Duncan KF
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- Catheterization, Female, Humans, Infant, Newborn, Male, Postoperative Period, Retrospective Studies, Aorta, Thoracic surgery, Cardiopulmonary Bypass, Circulatory Arrest, Deep Hypothermia Induced, Kidney physiology
- Abstract
Background: A clinically driven transition in perfusion technique occurred at Children's Hospital and Medical Center, Omaha, Nebraska, from primarily selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest to a technique of dual arterial perfusion including innominate artery and descending aortic cannulation (DAC), with continuous mildly hypothermic (>30 °C) full-flow cardiopulmonary bypass to the entire body. This study retrospectively compared outcomes in a recent cohort of neonates undergoing aortic arch reconstruction with the two techniques., Methods: The clinical records of 142 consecutive neonates undergoing operations involving aortic arch reconstruction at a single institution between April 2004 and September 2012 were reviewed. Renal function changes were graded according to the pediatric RIFLE score (based on risk, injury, failure, loss, and end-stage kidney disease). Sixteen patients, 8 supported with selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest and 8 with DAC, required immediate postoperative extracorporeal membrane oxygenation and were excluded from renal function analysis. Multivariable regression models evaluated predictors of pediatric RIFLE score., Results: Patients with DAC had shorter median bypass support (113 versus 172 minutes; p < 0.001) and myocardial ischemic time (43 versus 81 minutes; p < 0.001). Patients with DAC had less median fluid gain at 24 hours (37 versus 69 mL/kg; p < 0.001), and lower incidence of acute kidney injury (5% versus 31%; p < 0.001). Fewer patients with DAC (31% versus 58%; p = 0.001) required open chest. Use of selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest, single-ventricular physiology, and aortic cross-clamp time were found to be multivariable predictors of serious kidney dysfunction., Conclusions: Multisite arterial perfusion, including DAC, and maintenance of continuous mildly hypothermic full-flow cardiopulmonary bypass may offer advantages as a perfusion strategy for neonatal arch reconstruction. Prospective investigation of this technique is warranted., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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37. Descending aortic and innominate artery cannulation for aortic arch repair with mildly hypothermic continuous cardiopulmonary bypass in infants and children.
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Hammel JM, Deptula JJ, Siecke R, Abdullah I, and Duncan KF
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- Aorta, Thoracic abnormalities, Child, Child, Preschool, Humans, Infant, Perfusion methods, Aorta, Thoracic surgery, Brachiocephalic Trunk surgery, Cardiopulmonary Bypass methods, Hypothermia, Induced methods, Vascular Malformations surgery, Vascular Surgical Procedures methods
- Abstract
A technique is described for exposure of the descending aorta, allowing separate arterial cannulation for perfusion of the upper and lower body during reconstruction of the aortic arch, maintaining continuous full-flow cardiopulmonary bypass to the entire body. This single technique is applicable to all aortic arch pathologies and allows an unhurried aortic reconstruction in an unobstructed field.
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- 2013
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38. Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus.
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Hong Z, Kutty S, Toth PT, Marsboom G, Hammel JM, Chamberlain C, Ryan JJ, Zhang HJ, Sharp WW, Morrow E, Trivedi K, Weir EK, and Archer SL
- Subjects
- Animals, Animals, Newborn, Calcium metabolism, Cell Proliferation, Cells, Cultured, Ductus Arteriosus cytology, Dynamins, Female, Humans, Hydrogen Peroxide metabolism, Infant, Newborn, Male, Mitochondria metabolism, Models, Animal, Muscle, Smooth, Vascular cytology, Oxygen Consumption physiology, Rabbits, Tissue Culture Techniques, rho-Associated Kinases metabolism, Ductus Arteriosus physiology, GTP Phosphohydrolases physiology, Microtubule-Associated Proteins physiology, Mitochondrial Dynamics physiology, Mitochondrial Proteins physiology, Muscle, Smooth, Vascular physiology, Oxygen physiology, Vasoconstriction physiology
- Abstract
Rationale: Closure of the ductus arteriosus (DA) is essential for the transition from fetal to neonatal patterns of circulation. Initial PO2-dependent vasoconstriction causes functional DA closure within minutes. Within days a fibrogenic, proliferative mechanism causes anatomic closure. Though modulated by endothelial-derived vasodilators and constrictors, O2 sensing is intrinsic to ductal smooth muscle cells and oxygen-induced DA constriction persists in the absence of endothelium, endothelin, and cyclooxygenase mediators. O2 increases mitochondrial-derived H2O2, which constricts ductal smooth muscle cells by raising intracellular calcium and activating rho kinase. However, the mechanism by which oxygen changes mitochondrial function is unknown., Objective: The purpose of this study was to determine whether mitochondrial fission is crucial for O2-induced DA constriction and closure., Methods and Results: Using DA harvested from 30 term infants during correction of congenital heart disease, as well as DA from term rabbits, we demonstrate that mitochondrial fission is crucial for O2-induced constriction and closure. O2 rapidly (<5 minutes) causes mitochondrial fission by a cyclin-dependent kinase- mediated phosphorylation of dynamin-related protein 1 (Drp1) at serine 616. Fission triggers a metabolic shift in the ductal smooth muscle cells that activates pyruvate dehydrogenase and increases mitochondrial H2O2 production. Subsequently, fission increases complex I activity. Mitochondrial-targeted catalase overexpression eliminates PO2-induced increases in mitochondrial-derived H2O2 and cytosolic calcium. The small molecule Drp1 inhibitor, Mdivi-1, and siDRP1 yield concordant results, inhibiting O2-induced constriction (without altering the response to phenylephrine or KCl) and preventing O2-induced increases in oxidative metabolism, cytosolic calcium, and ductal smooth muscle cells proliferation. Prolonged Drp1 inhibition reduces DA closure in a tissue culture model., Conclusions: Mitochondrial fission is an obligatory, early step in mammalian O2 sensing and offers a promising target for modulating DA patency.
- Published
- 2013
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39. Two-stage biventricular rehabilitation for critical aortic stenosis with severe left ventricular dysfunction.
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Hammel JM, Duncan KF, Danford DA, and Kutty S
- Subjects
- Aortic Valve surgery, Aortic Valve Stenosis physiopathology, Humans, Infant, Infant, Newborn, Pulmonary Artery surgery, Retrospective Studies, Ventricular Dysfunction, Left physiopathology, Ventricular Function, Left physiology, Aortic Valve Stenosis surgery, Cardiac Surgical Procedures methods, Ventricular Dysfunction, Left surgery
- Abstract
Objectives: Critical aortic valve stenosis (CAS) in the newborn is treated by balloon or surgical aortic valve intervention with nearly equal success, but the subset of patients with severe left ventricular (LV) dilation and dysfunction present a significant mortality risk. We describe a two-stage surgical management approach for those infants who represent an unusually high failure risk for either aortic valvotomy or conventional stage 1 single ventricle (Norwood) palliation because of severe LV dysfunction at the time of presentation., Methods: A two-stage surgical palliation was undertaken consisting of surgical aortic valvotomy, bilateral pulmonary artery banding and atrial septectomy (stage 1), followed by patch closure of the atrial septal defect, ligation of the ductus arteriosus and removal of the pulmonary artery bands (stage 2) with prostaglandin infusion continued between stages to maintain right ventricular contribution to systemic perfusion via the ductus arteriosus., Results: Four neonates with CAS and severely depressed LV systolic function were treated using this strategy. LV dilation resolved and systolic function improved in three patients after 2, 2 and 4 weeks, enabling stage 2. LV dysfunction did not improve in one patient who expired before conversion to biventricular circulation. Of the three who proceeded to stage 2, one infant continued to have poor biventricular diastolic function that precluded conversion, and this patient also died. The remaining two infants are now alive and well at 34 and 44 months of age. These two had the most severe LV dilation (internal dimension Z-scores of 6.9 and 7.7) and the worst systolic function (fractional shortening 4 and 10%) at presentation, and both were born prematurely (32 and 35 weeks)., Conclusions: A two-stage surgical approach may improve the likelihood of survival in selected patients with CAS presenting with severely depressed LV systolic function. Relief of LV distention may have contributed to the improvement of LV function in these infants.
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- 2013
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40. Safety of cardiac magnetic resonance and contrast angiography for neonates and small infants: a 10-year single-institution experience.
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Rangamani S, Varghese J, Li L, Harvey L, Hammel JM, Fletcher SE, Duncan KF, Danford DA, and Kutty S
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- Comorbidity, Contrast Media, Female, Humans, Incidence, Infant, Infant, Newborn, Longitudinal Studies, Male, Nebraska epidemiology, Retrospective Studies, Risk Assessment, Anesthetics, General therapeutic use, Bradycardia epidemiology, Drug-Related Side Effects and Adverse Reactions epidemiology, Gadolinium, Hypothermia epidemiology, Magnetic Resonance Angiography statistics & numerical data, Magnetic Resonance Imaging, Cine statistics & numerical data
- Abstract
Background: With increasing applications of cardiac magnetic resonance (CMR) and magnetic resonance angiography (MRA) for evaluation of congenital heart disease (CHD), safety of this technology in the very young is of particular interest., Objective: We report our 10-year experience with CMR in neonates and small infants with particular focus on the safety profile and incidence of adverse events (AEs)., Materials and Methods: We reviewed clinical, anesthesia and nursing records of all children ≤120 days of age who underwent CMR. We recorded variables including cardiac diagnosis, study duration, anesthesia type and agents, prostaglandin E1 (PGE1) dependence and gadolinium (Gd) use. Serially recorded temperature, systemic saturation (SpO(2)) and cardiac rhythm were analyzed. Primary outcome measure was any AE during or <24 h after the procedure, including minor AEs such as hypothermia (axillary temperature ≤95 °F), desaturation (SpO(2) drop ≥10% below baseline) and bradycardia (heart rate ≤100 bpm). Secondary outcome measure was unplanned overnight hospitalization of outpatients., Results: Children (n = 143; 74 boys, 69 girls) had a median age of 6 days (1-117), and 98 were ≤30 days at the time of CMR. The median weight was 3.4 kg (1.4-6 kg) and body surface area 0.22 m(2) (0.13-0.32 m(2)). There were 118 (83%) inpatients (108 receiving intensive care) and 25 (17%) outpatients. Indications for CMR were assessment of aortic arch (n = 57), complex CHD (n = 41), pulmonary veins (n = 15), vascular ring (n = 8), intracardiac mass (n = 8), pulmonary artery (n = 7), ventricular volume (n = 4), and systemic veins (n = 3). CMR was performed using a 1.5-T scanner and a commercially available coil. CMR utilized general anesthesia (GA) in 86 children, deep sedation (DS) in 50 and comforting methods in seven. MRA was performed in 136 children. Fifty-nine children were PGE1-dependent and 39 had single-ventricle circulation. Among children on PGE1, 43 (73%) had GA and 10 (17%) had DS. Twelve children (9%) had adverse events (AEs)-one major and 11 minor. Of those 12, nine children had GA (10%) and three had DS (6%). The single major AE was respiratory arrest after DS in a neonate (resuscitated without sequelae). Minor AEs included desaturations (n = 2), hypothermia (n = 5), bradycardia (n = 2), and bradycardia with hypoxemia (n = 2). Incidence of minor AEs was 9% for inpatients (vs. 4% for outpatients), and 8% for neonates (vs. 9% for age ≥30 days). Incidence of minor AEs was similar between PGE1-dependent infants and the non-PGE1 group. There were no adverse events related to MRA. Of 25 outpatients, 5 (20%) were admitted for overnight observation due to desaturations., Conclusion: CMR and MRA can be accomplished safely in neonates and infants ≤120 days old for a wide range of pre-surgical cardiac indications. Adverse events were unrelated to patient age, complexity of heart disease, type of anesthesia or PGE1 dependence.
- Published
- 2012
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41. "Closed-vein" technique for primary sutureless repair of anomalous pulmonary venous connection.
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Hammel JM, Hunt PW, Abdullah I, and Duncan KF
- Subjects
- Anastomosis, Surgical methods, Cardiopulmonary Bypass methods, Heart Atria surgery, Humans, Risk Assessment, Suture Techniques, Sutures, Treatment Outcome, Arteriovenous Malformations surgery, Pulmonary Veins abnormalities, Pulmonary Veins surgery, Vascular Surgical Procedures methods
- Abstract
Deep hypothermic circulatory arrest or low-flow bypass are commonly used in primary repair of total anomalous pulmonary venous connection, or individual veins may be dissected to allow clamp or snare application, in order to provide a bloodless field for anastomosis by the direct or sutureless marsupialization technique. In the described technical modification, the marsupialization of the opened atrium to the posterior pericardium is completed before opening the pulmonary venous confluence, allowing bloodless exposure during full-flow normothermic bypass. In addition, vein branch dissection is avoided., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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42. Serial assessment of right ventricular volume and function in surgically palliated hypoplastic left heart syndrome using real-time transthoracic three-dimensional echocardiography.
- Author
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Kutty S, Graney BA, Khoo NS, Li L, Polak A, Gribben P, Hammel JM, Smallhorn JF, and Danford DA
- Subjects
- Computer Systems, Female, Humans, Infant, Infant, Newborn, Male, Palliative Care, Reproducibility of Results, Sensitivity and Specificity, Ventricular Dysfunction, Right physiopathology, Echocardiography, Three-Dimensional methods, Hypoplastic Left Heart Syndrome diagnostic imaging, Hypoplastic Left Heart Syndrome surgery, Stroke Volume, Ventricular Dysfunction, Right diagnostic imaging, Ventricular Dysfunction, Right surgery
- Abstract
Background: Right ventricular (RV) failure is a major cause of morbidity and mortality in patients with hypoplastic left heart syndrome (HLHS), but the longitudinal course of RV volumes through staged palliation (SP) has not been previously investigated. The aim of this study was to evaluate RV volume and function longitudinally through SP of HLHS using real-time three-dimensional echocardiography., Methods: A total of 18 subjects with HLHS were prospectively studied at four time points from diagnosis through stage 2 (SP2). Real-time three-dimensional echocardiographic full-volume data sets were acquired in high-frame rate mode with electrocardiographic gating. Volumetric and functional analyses were performed using a semiautomatic contour detection algorithm. Eighteen age-matched and sex-matched normal infants (aged 0-6 months) were studied at comparable time points as controls., Results: Presurgical examinations (pre-stage 1 [SP1]; n = 18) were performed at a mean age of 4 days, post-SP1 examinations (n = 17) at a mean age of 20 days, pre-SP2 examinations (n = 14) at a mean age of 4.6 months, and post-SP2 examinations (n = 14) at a mean age of 5.5 months, constituting a total of 63 examinations. The mean values of RV end-diastolic volume indexed to body surface area (EDVi) at the four time points were 87 ± 30, 104 ± 39, 112 ± 34, and 102 ± 35 mL/m(2), respectively. There was an increase in EDVi (P = .024) from pre-SP1 to post-SP1 but no significant change between post-SP1 and pre-SP2. The decrease in EDVi after SP2 did not reach statistical significance. Mean RV ejection fractions (EFs) were 50 ± 5%, 45 ± 5%, 46 ± 5%, and 38 ± 4%, respectively. There was a trend toward decreasing EF throughout SP, with statistically significant decreases from pre-SP1 to post-SP1 (P = .003) and from pre-SP2 to post-SP2 (P < .001). In normal infants, the mean RV EDVi was 50 ± 10 mL/m(2) (approximately half that of patients with HLHS), and the mean EF was 51 ± 3%. There was good interobserver agreement for EDVi, end-systolic volume indexed to body surface area, and EF., Conclusions: Real-time three-dimensional echocardiography is a reproducible means for evaluating RV volumes and EFs in patients with HLHS. Indexed RV diastolic volume remains stable to slightly increased, and RV EF deteriorates as the first two stages of surgical palliation are accomplished. The findings of this study highlight the adverse physiology of HLHS, which deteriorates even among early survivors despite SP., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)
- Published
- 2012
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43. Microbubble mediated thrombus dissolution with diagnostic ultrasound for the treatment of chronic venous thrombi.
- Author
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Kutty S, Wu J, Hammel JM, Xie F, Gao S, Drvol LK, Lof J, Radio SJ, Therrien SL, Danford DA, and Porter TR
- Subjects
- Animals, Blood Platelets diagnostic imaging, Catheter Ablation, Central Venous Catheters, Chronic Disease, Electrocardiography, Feasibility Studies, Fluoroscopy, Heart physiopathology, Hemodynamics, Radionuclide Imaging, Sus scrofa, Ultrasonography, Venous Thrombosis physiopathology, Venous Thrombosis surgery, Microbubbles, Venous Thrombosis diagnostic imaging, Venous Thrombosis therapy
- Abstract
Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo., Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2) respectively in Group A; compared to 0.24 and 0.21 cm(2) in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment., Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.
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- 2012
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44. Hybrid peratrial double device closure of a patent foramen ovale and sinus venosus defect in an infant with vein of Galen malformation.
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Delaney JW, Thorell WE, and Hammel JM
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- Echocardiography, Transesophageal, Female, Foramen Ovale, Patent complications, Foramen Ovale, Patent diagnosis, Heart Septal Defects, Atrial complications, Heart Septal Defects, Atrial diagnosis, Humans, Infant, Magnetic Resonance Imaging, Prosthesis Design, Scimitar Syndrome complications, Time Factors, Treatment Outcome, Vein of Galen Malformations complications, Vein of Galen Malformations diagnosis, Abnormalities, Multiple, Cardiac Catheterization instrumentation, Foramen Ovale, Patent therapy, Heart Septal Defects, Atrial therapy, Septal Occluder Device, Vein of Galen Malformations therapy
- Abstract
Vein of Galen aneurysmal malformation is the most common cerebral arteriovenous malformation in children. Neurointerventional embolization has improved outcomes with this lesion. An association with cardiac defects has been recognized and can increase the risk of systemic embolic events during treatment. Cardiopulmonary bypass (CPB) to correct the cardiac defect before repair of the malformation may be associated with compromised cerebral perfusion and possible neurologic injury. We describe a successful hybrid peratrial closure of two intracardiac shunts (a patent foramen ovale and a sinus venosus ASD) before neurointervention, avoiding CPB, and eliminating the intracardiac embolic risk during treatment of the vein of Galen malformation., (Copyright © 2011 Wiley Periodicals, Inc.)
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- 2011
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45. Sonothrombolysis of intra-catheter aged venous thrombi using microbubble enhancement and guided three-dimensional ultrasound pulses.
- Author
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Kutty S, Xie F, Gao S, Drvol LK, Lof J, Fletcher SE, Radio SJ, Danford DA, Hammel JM, and Porter TR
- Subjects
- Animals, Contrast Media administration & dosage, Disease Models, Animal, Equipment Design, Feasibility Studies, Imaging, Three-Dimensional, In Vitro Techniques, Infusions, Intravenous, Microbubbles, Phantoms, Imaging, Swine, Ultrasonography, Interventional, Venous Thrombosis diagnostic imaging, Catheterization, Central Venous adverse effects, Ultrasonic Therapy methods, Venous Thrombosis therapy
- Abstract
Background: Central venous and arterial catheters are a major source of thromboembolic disease in children. The investigators hypothesized that guided high-mechanical index (MI) impulses from diagnostic three-dimensional (3D) ultrasound during an intravenous microbubble infusion could dissolve these thrombi., Methods: An in vitro system simulating intracatheter thrombi was created and then treated with guided high-MI impulses from 3D ultrasound, using low-MI microbubble sensitive imaging pulse sequence schemes to detect the microbubbles. Ten aged thrombi >24 hours old were tested using 3D ultrasound coupled with a continuous diluted microbubble infusion (group A) and 10 with 3D ultrasound alone (group B)., Results: The mean thrombus age was 28.6 hours (range, 26.6-30.3 hours). Group A exhibited a 55 +/- 19% reduction in venous thrombus size compared with 31 +/- 10% in group B (P = .008). Feasibility testing was performed in four pigs, establishing an in vivo model to investigate further the efficacy of this approach., Conclusions: Sonothrombolysis of aged intracatheter venous thrombi can be achieved with commercially available microbubbles and guided high-MI ultrasound from a diagnostic 3D transducer., (2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)
- Published
- 2010
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46. Anoxic ventilation improves systemic perfusion during extracorporeal circulation with uncontrolled systemic-to-pulmonary shunt.
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Hammel JM, Deptula J, Hunt PW, Lang H, and Duncan KF
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- Animals, Atrial Function physiology, Blood Pressure, Extracorporeal Circulation instrumentation, Oxygen metabolism, Oxyhemoglobins analysis, Swine, Weaning, Cardiopulmonary Bypass methods, Extracorporeal Circulation methods, Oxygen administration & dosage, Perfusion methods, Pulmonary Ventilation
- Abstract
Uncontrolled systemic-to-pulmonary shunt results in decreased systemic flow during extracorporeal life support (ECLS). Ligation of systemic-to-pulmonary shunts during ECLS is associated with poor outcome and is not always readily achieved. In ex vivo preparations, alveolar hypoxia results in pulmonary vasoconstriction despite normoxic pulmonary perfusate. We hypothesized that anoxic ventilation would result in reduced pulmonary shunting and increased systemic flow during ECLS in piglets with systemic-to-pulmonary shunt. Four piglets were placed on ECLS with right and left atrial drainage. A shunt was created between the bicarotid trunk and pulmonary artery, using 5-mm ePTFE tubing. Inspired oxygen was reduced to <1% for 10 minutes, then returned to room air; pH, hematocrit, temperature, ventilatory pressures, and total pump flow were maintained constant. Systemic arterial pressure and right atrial return volume and hemoglobin saturation were measured: All decreased significantly upon shunt unclamping. Anoxic ventilation caused increased systemic pressure (34 vs. 28 mm Hg, p < 0.05), flow (335 vs. 278 mL/min, p < 0.05), and systemic venous saturation (53% vs. 48%, p = 0.13) compared with room air ventilation. In conclusion, anoxic ventilation during normoxic ECLS in subjects with systemic-to-pulmonary shunts results in a significant and potentially clinically useful reduction in pulmonary shunting.
- Published
- 2007
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47. Preservation of mitochondrial structure and function after cardioplegic arrest in the neonate using a selective mitochondrial KATP channel opener.
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Wang L, Kinnear C, Hammel JM, Zhu W, Hua Z, Mi W, and Caldarone CA
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- Adenosine Triphosphate analysis, Animals, Animals, Newborn, Apoptosis physiology, Cytochromes c metabolism, Hemodynamics, Oxygen Consumption, Potassium Channels, Swine, Translocation, Genetic, Diazoxide pharmacology, Heart Arrest, Induced, Mitochondria, Heart physiology, Mitochondria, Heart ultrastructure, Vasodilator Agents pharmacology
- Abstract
Background: Mitochondrial dysfunction may contribute to early postoperative neonatal heart dysfunction. Diazoxide, a mitochondrial-selective adenosine triphosphate-sensitive potassium-channel opener, is associated with mitochondrial preservation after cardioplegic arrest. We evaluated the mitochondrial-protective effect of diazoxide in terms of mitochondrial structure and function after neonatal cardioplegic arrest., Methods: Newborn piglets (age, approximately 14 days) underwent cardiopulmonary bypass and 60 minutes of cardioplegic arrest using cold crystalloid cardioplegic solution (CCP, n = 5) or cold crystalloid cardioplegic solution with diazoxide (CCP+D, n = 5). After 6 hours of recovery, myocardium was harvested. Control myocardium from piglets that did not undergo cardiopulmonary bypass (non-CPB, n = 5) was obtained., Results: Cardioplegic arrest was associated with translocation of Bax to the mitochondria, which was not prevented by diazoxide. Nevertheless, by electron microscopy, CCP-associated remodeling of mitochondrial structure was subjectively diminished in CCP+D hearts. In addition, CCP-associated mitochondrial permeabilization and cytochrome c release into the cytosol were prevented with CCP+D (p < 0.05). In vitro oxygen consumption of isolated mitochondria demonstrated deficient function of mitochondrial complex I in CCP, but it was preserved in the CCP+D myocardial mitochondria (p < 0.05). Complex II and IV activity was not different among groups. In parallel with impaired complex I function, the cardiac adenosine triphosphate content was diminished in CCP hearts, but well maintained in CCP+D hearts (p < 0.05)., Conclusions: Although early apoptotic signaling events (Bax translocation) are not prevented by diazoxide, addition of the mitochondrial-selective adenosine triphosphate-sensitive potassium-channel opener to the cardioplegic solution is associated with protection of mitochondrial structural and functional integrity in a clinically relevant model of neonatal cardiac surgery. The mitochondrial-protective effects of diazoxide may contribute to improved postoperative myocardial function in the neonate.
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- 2006
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48. Septic arthritis of the acromioclavicular joint.
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Hammel JM and Kwon N
- Subjects
- Acromioclavicular Joint diagnostic imaging, Acute Disease, Aged, Arthritis, Infectious physiopathology, Humans, Magnetic Resonance Imaging, Male, Shoulder Pain etiology, Ultrasonography, Acromioclavicular Joint pathology, Arthritis, Infectious diagnosis, Shoulder Pain diagnosis
- Abstract
Septic arthritis of the acromioclavicular (AC) joint is a rare but rapidly destructive etiology of acute shoulder pain. We report a case of septic AC joint in the absence of trauma or intravenous drug use. A diabetic man presented with severe right shoulder pain and was later diagnosed with septic arthritis of the AC joint by magnetic resonance imaging (MRI) and positive blood cultures. Chronic diabetic foot ulcers were the source of the patient's group B streptococcus bacteremia.
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- 2005
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49. Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart.
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Caldarone CA, Barner EW, Wang L, Karimi M, Mascio CE, Hammel JM, Segar JL, Du C, and Scholz TD
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- Animals, Animals, Newborn, Disease Models, Animal, Immunohistochemistry, Myocardium metabolism, Oxygen Consumption, Permeability, Proto-Oncogene Proteins c-bcl-2 metabolism, Sheep, bcl-2-Associated X Protein, Apoptosis, Mitochondria metabolism, Mitochondria ultrastructure, Mitochondrial Diseases pathology, Mitochondrial Diseases physiopathology, Myocardium ultrastructure
- Abstract
Background: In the early postoperative period, the neonatal myocardium undergoes sparse apoptotic cell loss ( approximately 1% of myocytes). Because apoptosis is preceded by events associated with mitochondrial dysfunction, the fraction of myocytes with preapoptotic mitochondrial changes has important clinical implications (eg, postoperative myocardial dysfunction). My colleagues and I therefore hypothesized that postoperative apoptotic myocytes represent a tip of the iceberg, with more myocytes upstream with apoptosis-related mitochondrial dysfunction (ARMD)., Methods: Neonatal lambs underwent cardiopulmonary bypass, 60 minutes of cardioplegic arrest, and 6 hours of recovery (cardiopulmonary bypass with cardioplegic arrest [CPB+CP]; n = 5) and were compared with nonbypass controls (non-CPB; n = 5). Myocardium (left ventricle [LV] and right ventricle [RV]) was examined by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, electron microscopy, immunohistochemistry, Western blot, and isolated mitochondrial oxygen consumption measurement., Results: TUNEL-positive nuclei and electron microscopy-confirmed mitochondrial structural changes were more common in CPB+CP than non-CPB myocardium and were more common in the LV than RV (p = 0.0016). Bax (a proapoptotic mediator) translocated from the cytosol to the mitochondria (LV > RV; p < 0.05). Immunohistochemistry demonstrated diffuse mitochondrial loss of cytochrome c that was consistent with outer mitochondrial membrane permeabilization (LV > RV > non-CPB). Permeabilization was further demonstrated by augmentation of oxygen consumption in isolated mitochondria after administration of exogenous cytochrome c. The mitochondrial oxygen consumption boost was 57% for CPB+CP:LV; 23% for CPB+CP:RV; and 18% and 17% for non-CPB:LV and non-CPB:RV, respectively (p < 0.01, CPB+CP:LV vs other groups)., Conclusions: ARMD is much greater than the prevalence of TUNEL-positive myocytes in postoperative neonatal myocardium. Greater LV vulnerability may represent a relationship between increased afterload and ARMD. These changes are consistent with the early postoperative myocardial dysfunction commonly reported after neonatal cardiac operations.
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- 2004
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50. Neonatal vulnerability to ischemia and reperfusion: Cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs.
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Karimi M, Wang LX, Hammel JM, Mascio CE, Abdulhamid M, Barner EW, Scholz TD, Segar JL, Li WG, Niles SD, and Caldarone CA
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- Animals, Apoptosis physiology, Blotting, Western, Caspases metabolism, Cytochrome c Group metabolism, Disease Models, Animal, Electron Transport Complex IV metabolism, Enzyme Activation physiology, Fluorescent Dyes, Heart Arrest, Induced adverse effects, Heart Ventricles pathology, In Situ Nick-End Labeling, Indoles, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases metabolism, Models, Cardiovascular, Myocardial Reperfusion Injury physiopathology, Myocardium cytology, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac metabolism, Oxidative Stress physiology, Proto-Oncogene Proteins metabolism, Sheep, Animals, Newborn physiology, Myocardial Reperfusion Injury etiology
- Abstract
Objectives: Apoptosis is a mechanism for deletion of injured or obsolete cells that is distinct from necrosis and mediated by mitochondrial release of cytochrome c caspase activation. Because myocardial apoptosis is a part of normal fetal and postnatal maturation, we hypothesize that neonatal myocardium is more vulnerable to undergo myocardial apoptosis than mature myocardium after cardioplegic arrest., Methods: Newborn and mature lambs (n = 5 in each group) underwent cardiopulmonary bypass, antegrade crystalloid hyperkalemic cardioplegic arrest for 60 minutes, and a 6-hour recovery period. Myocardium was examined by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL), Western blotting, in vitro kinase assays, and fluorometric assays of the activity of caspases 3, 8, and 9. Myocardium from nonoperated control subjects (n = 5 in each age group) was also obtained., Results: More TUNEL-positive nuclei were present in the newborn postcardioplegic myocardium (P =.04). Caspase 3, 8, and 9 activities were 1.6-fold, 1.5-fold, and 1.4-fold greater in the newborn postcardioplegic myocardium (P =.04, P =.01, and P =.01, respectively). The Bax/Bcl-2 ratio was higher in the newborn postcardioplegic myocardium (P =.04). Apoptosis signal-regulating kinase 1 activity and cleaved caspase 3 levels were higher in the newborn postcardioplegic myocardium (P =.02 and P =.009). Mitochondrial release of cytochrome c was greater in the newborn postcardioplegic myocardium (P =.009)., Conclusions: The increased Bax/Bcl-2 ratio in the newborn myocardium suggests a proapoptotic state that is manifested by greater TUNEL staining, cytochrome c release, and cleavage of caspase 3. Increased apoptosis signal-regulating kinase 1 activity suggests greater oxidative stress, immature mechanisms to ameliorate oxidative stress, or both in the neonatal myocardium. Mitochondrial release of cytochrome c suggests that apoptosis-related mitochondrial dysfunction might contribute to early postoperative myocardial dysfunction in the neonate.
- Published
- 2004
- Full Text
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