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1.
Artif Organs ; 44(6): E226-E237, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31876310

RESUMO

Mechanical circulatory support (MCS) devices continue to be hampered by thrombotic adverse events (AEs), a consequence of device-imparted supraphysiologic shear stresses, leading to shear-mediated platelet activation (SMPA). In advancing MCS devices from design to clinical use, in vitro circulatory loops containing the device under development and testing are utilized as a means of assessing device thrombogenicity. Physical characteristics of these test circulatory loops may also contribute to inadvertent platelet activation through imparted shear stress, adding inadvertent error in evaluating MCS device thrombogenicity. While investigators normally control for the effect of a loop, inadvertent addition of what are considered innocuous connectors may impact test results. Here, we tested the effect of common, additive components of in vitro circulatory test loops, that is, connectors and loop geometry, as to their additive contribution to shear stress via both in silico and in vitro models. A series of test circulatory loops containing a ventricular assist device (VAD) with differing constituent components, were established in silico including: loops with 0~5 Luer connectors, a loop with a T-connector creating 90° angulation, and a loop with 90° angulation. Computational fluid dynamics (CFD) simulations were performed using a k - ω shear stress transport turbulence model to platelet activation index (PAI) based on a power law model. VAD-operated loops replicating in silico designs were assembled in vitro and gel-filtered human platelets were recirculated within (1 hour) and SMPA was determined. CFD simulations demonstrated high shear being introduced at non-smooth regions such as edge-connector boundaries, tubing, and at Luer holes. Noticeable peaks' shifts of scalar shear stress (sss) distributions toward high shear-region existed with increasing loop complexity. Platelet activation also increased with increasing shear exposure time, being statistically higher when platelets were exposed to connector-employed loop designs. The extent of platelet activation in vitro could be successfully predicted by CFD simulations. Loops employing additional components (non-physiological flow pattern connectors) resulted in higher PAI. Loops with more components (5-connector loop and 90° T-connector) showed 63% and 128% higher platelet activation levels, respectively, versus those with fewer (0-connector (P = .023) and a 90° heat-bend loop (P = .0041). Our results underscore the importance of careful consideration of all component elements, and suggest the need for standardization in designing in vitro circulatory loops for MCS device evaluation to avoid inadvertent additive SMPA during device evaluation, confounding overall results. Specifically, we caution on the use and inadvertent introduction of additional connectors, ports, and other shear-generating elements which introduce artifact, clouding primary device evaluation via introduction of additive SMPA.


Assuntos
Desenho de Equipamento , Coração Auxiliar/efeitos adversos , Hemodinâmica/fisiologia , Trombose/prevenção & controle , Adulto , Artefatos , Plaquetas/fisiologia , Simulação por Computador , Voluntários Saudáveis , Humanos , Ativação Plaquetária/fisiologia , Resistência ao Cisalhamento , Estresse Mecânico , Trombose/etiologia
2.
J Surg Res ; 233: 376-380, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502274

RESUMO

BACKGROUND: To avoid the radiation exposure of CT imaging and the expense of CT or MRI studies, we sought to develop a non-radiographic severity measurement of pectus excavatum based on 3D photogrammetric imaging. METHODS: Over 28 mo, ten consecutive patient volunteers with pectus excavatum underwent 3D stereophotogrammetric imaging. The surface width to surface depth ratio (Surface Lengths Pectus Index), the chest deformity's surface area to total chest surface area (Pectus Surface Area Ratio), and the chest deformity's volume to total chest volume (Pectus Volume Ratio) were calculated. Simple linear regression analysis compared the Surface Lengths Pectus Index, Pectus Surface Area Ratio, and Pectus Volume Ratio calculations each to the corresponding known CT pectus index. RESULTS: The correlation between CT pectus index versus Surface Lengths Pectus Index yielded an R-squared value of 0.7637 and a P value of 0.0013. A CT pectus index of 3.4 or greater (eight patients) corresponded to a Surface Lengths Pectus Index of 1.86 or greater (six patients). The CT pectus index versus Pectus Surface Area Ratio (R-squared = 0.4627, P = 0.0305) and the CT pectus index versus the Pectus Volume Ratio (R-squared = 0.3048, P = 0.0990) demonstrated less correlation. CONCLUSION: Surface Lengths Pectus Index corresponds to the CT pectus index and may be adequate to determine severity of pectus excavatum in some patients.


Assuntos
Tórax em Funil/diagnóstico por imagem , Imageamento Tridimensional/métodos , Fotogrametria , Adolescente , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
3.
Surg Clin North Am ; 102(5): 759-778, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36209744

RESUMO

Esophageal atresia (EA) with tracheoesophageal fistula (TEF) is among the most common congenital anomalies requiring surgical intervention in infancy. General surgeons practicing in rural or austere environments may encounter emergency situations requiring their involvement. Respiratory emergencies can arise in the neonatal period; the recommended approaches are the ligation of the fistula through the chest or occlusion of the distal esophagus through the abdomen. As survivors of the condition reach late adulthood, general surgeons can anticipate encountering these patients. An understanding of risk factors, common symptoms, associated anomalies, and the appropriate diagnostic evaluation will facilitate care.


Assuntos
Atresia Esofágica , Cirurgiões , Fístula Traqueoesofágica , Adulto , Atresia Esofágica/complicações , Atresia Esofágica/diagnóstico , Atresia Esofágica/cirurgia , Humanos , Recém-Nascido , Fístula Traqueoesofágica/complicações , Fístula Traqueoesofágica/diagnóstico , Fístula Traqueoesofágica/cirurgia , Resultado do Tratamento
4.
Thromb Haemost ; 120(5): 776-792, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369849

RESUMO

BACKGROUND: Implantable cardiovascular therapeutic devices, while hemodynamically effective, remain limited by thrombosis. A driver of device-associated thrombosis is shear-mediated platelet activation (SMPA). Underlying mechanisms of SMPA, as well as useful biomarkers able to detect and discriminate mechanical versus biochemical platelet activation, are poorly defined. We hypothesized that SMPA induces a differing pattern of biomarkers compared with biochemical agonists. METHODS: Gel-filtered human platelets were subjected to mechanical activation via either uniform constant or dynamic shear; or to biochemical activation by adenosine diphosphate (ADP), thrombin receptor-activating peptide 6 (TRAP-6), thrombin, collagen, epinephrine, or arachidonic acid. Markers of platelet activation (P-selectin, integrin αIIbß3 activation) and apoptosis (mitochondrial membrane potential, caspase 3 activation, and phosphatidylserine externalization [PSE]) were examined using flow cytometry. Platelet procoagulant activity was detected by chromogenic assay measuring thrombin generation. Contribution of platelet calcium flux in SMPA was tested employing calcium chelators, ethylenediaminetetraacetic acid (EDTA), and BAPTA-AM. RESULTS: Platelet exposure to continuous shear stress, but not biochemical agonists, resulted in a dramatic increase of PSE and procoagulant activity, while no integrin αIIbß3 activation occurred, and P-selectin levels remained barely elevated. SMPA was associated with dissipation of mitochondrial membrane potential, but no caspase 3 activation was observed. Shear-mediated PSE was significantly decreased by chelation of extracellular calcium with EDTA, while intracellular calcium depletion with BAPTA-AM had no significant effect. In contrast, biochemical agonists ADP, TRAP-6, arachidonic acid, and thrombin were potent inducers of αIIbß3 activation and/or P-selectin exposure. This differing pattern of biomarkers seen for SMPA for continuous uniform shear was replicated in platelets exposed to dynamic shear stress via circulation through a ventricular assist device-propelled circulatory loop. CONCLUSION: Elevated shear stress, but not biochemical agonists, induces a differing pattern of platelet biomarkers-with enhanced PSE and thrombin generation on the platelet surface. This differential biomarker phenotype of SMPA offers the potential for early detection and discrimination from that mediated by biochemical agonists.


Assuntos
Plaquetas/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Mecanotransdução Celular , Ativação Plaquetária/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/patologia , Caspase 3/sangue , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Selectina-P/sangue , Fosfatidilserinas/sangue , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Estresse Mecânico
5.
J Pediatr Surg ; 48(1): 67-73, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23331795

RESUMO

BACKGROUND: Recent breakthroughs have allowed for production of plasma at room temperature. Cold atmospheric plasma (CAP) may offer the capability of delivering reactive oxygen species directly into tissues, representing a novel modality for targeted cancer therapy. We studied helium-based CAP's effect on neuroblastoma, both in-vitro and in an in-vivo murine model. METHODS: Mouse neuroblastoma cultures were treated with CAP for 0, 30, 60, and 120 s and assayed for apoptotic and metabolic activity immediately and at 24 and 48 h post-treatment. Five-millimeter tumors were ablated with a single transdermal CAP treatment, and tumor volume and mouse survival were measured. RESULTS: CAP decreased metabolic activity, induced apoptosis, and reduced viability of cancer cells in proportion to both duration of exposure and time post-treatment. In-vivo, a single treatment ablated tumors and eventual tumor growth was decelerated. Furthermore, survival nearly doubled, with median survival of 15 vs. 28 days (p<0.001). CONCLUSIONS: Our findings demonstrate the sensitivity of neuroblastoma to CAP treatment, both in-vitro and in an in-vivo mouse model of established tumor. While further investigation is necessary to establish the mechanism and optimize the treatment protocol, these initial observations establish cold atmospheric plasma as a potentially useful ablative therapy in neuroblastoma.


Assuntos
Técnicas de Ablação/métodos , Hélio/uso terapêutico , Neuroblastoma/cirurgia , Gases em Plasma/uso terapêutico , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Estimativa de Kaplan-Meier , Camundongos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Distribuição Aleatória , Resultado do Tratamento
6.
J Pediatr Surg ; 47(4): 652-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22498377

RESUMO

PURPOSE: Surgical organizations have begun to focus their efforts on providing humanitarian assistance in international communities. Most surgeons do not have previous international experience and lack an understanding of what is expected and what care they can provide. The unknown factors include case types, patient volume, postoperative care, and equipment. This abstract presents humanitarian assistance mission and highlights the importance of preparation, host nation involvement, and understanding the local politics of each country. METHODS: In April to July 2009, the USNS (United States Naval Ship) Comfort deployed to provide humanitarian assistance to 7 countries through Central and South America. Data collected included numbers and types of procedures, rate of rejection of patients for operation, patient age, American Society of Anesthesiology (ASA) score, and length of procedure. RESULTS: These data represent the total mission of Continuing Promise 2009 including a total of 1137 surgical procedures of which 340 were pediatric (<18 years old). The average number of pediatric cases for each country in 7 days was 48.3 ± 21.4, with a range of 24 to 84. The average age was 7.5 years (range, 1 month to 18 years). In partnership with host physicians, preoperative screening occurred over 2 to 3 days for every 7 operative days. We maintained a low threshold for rejection (rate of 43%; range, 21%-62%) and average ASA score of 1.3. Including all pediatric subspecialties, the most frequent procedures were inguinal (23%) and umbilical (14%) hernias. Although these were the most frequent procedure, the range and variety of cases varied widely. We had a very low early complication rate (1.2%), including 3 wound infections and 1 early hernia recurrence. CONCLUSIONS: Our data represent the largest collection to date on the pediatric surgical care of children in a humanitarian effort. Our experience can be used to identify the most likely types of cases in South and Central America and as a model for the safe and efficient treatment of children in a developing country.


Assuntos
Cirurgia Geral , Missões Médicas/organização & administração , Pediatria , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , América Central , Criança , Pré-Escolar , Humanos , Lactente , Missões Médicas/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , América do Sul , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Estados Unidos
7.
Disaster Med Public Health Prep ; 6(4): 370-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23241468

RESUMO

OBJECTIVE: The Haitian earthquake of January 12, 2010, was a disaster essentially unprecedented in the Western Hemisphere's recorded history. The USNS Comfort departed from Baltimore, Maryland, within 72 hours of the earthquake and arrived in Port-au-Prince harbor on January 19. During the subsequent 40 days, the ship provided one of the largest relief efforts in the US Navy's history. METHODS: The data analyzed included all patients evaluated and treated by the USNS Comfort between January 19 and February 27, 2010. A medical chart with a unique identifier was created for each patient on admission. A patient database was created from these records and used for this analysis. RESULTS: A total of 872 patients and 185 patient escorts were processed aboard the ship. Ages ranged from younger than 1 day to 89 years: 635 were adults and 237 were children. Of those admitted, 817 of the patients were admitted for longer than 24 hours; the average length of stay was 8.0 days. The need for surgery was substantial: 454 patients went to the operating room (OR) 843 times for 927 cumulative procedures. A total of 58 patients underwent amputations. CONCLUSIONS: Haiti was almost completely reliant on foreign medical teams for trauma care. Analysis of the data illustrates the challenges of triage and treatment in a humanitarian mass-casualty response. The remarkable coordination and cooperation among the Haitian Ministry of Health, nongovernmental humanitarian aid organizations, and the US military highlighted the responders' respective capabilities and demonstrated the importance of collaboration in future disaster response efforts.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Terremotos , Hospitais Militares/estatística & dados numéricos , Socorro em Desastres/estatística & dados numéricos , Adolescente , Adulto , Idoso , Baltimore , Criança , Pré-Escolar , Feminino , Haiti , Humanos , Lactente , Recém-Nascido , Masculino , Incidentes com Feridos em Massa , Pessoa de Meia-Idade , Navios , Triagem/estatística & dados numéricos , Adulto Jovem
8.
Immunotargets Ther ; 1: 13-23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-27471682

RESUMO

Toll-like receptor (TLR) agonists represent potentially useful cancer vaccine adjuvants in their ability to stimulate antigen-presenting cells (APCs) and subsequently amplify the cytotoxic T-cell response. The purpose of this study was to characterize APC responses to TLR activation and to determine the subsequent effect on lymphocyte activation. We exposed murine primary bone marrow-derived macrophages to increasing concentrations of agonists to TLRs 2, 3, 4, and 9. This resulted in a dose-dependent increase in production of not only tumor necrosis factor-alpha (TNF-α), a surrogate marker of the proinflammatory response, but also interleukin 10 (IL-10), a well-described inhibitory cytokine. Importantly, IL-10 secretion was not induced by low concentrations of TLR agonists that readily produced TNF-α. We subsequently stimulated lymphocytes with anti-CD3 antibody in the presence of media from macrophages activated with higher doses of TLR agonists and observed suppression of interferon gamma release. Use of both IL-10 knockout macrophages and IL-10 small-interfering RNA (siRNA) ablated this suppressive effect. Finally, IL-10 siRNA was successfully used to suppress CpG-induced IL-10 production in vivo. We conclude that TLR-mediated APC stimulation can induce a paradoxical inhibitory effect on T-cell activation mediated by IL-10.

9.
J Pediatr Surg ; 46(10): 1978-84, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22008338

RESUMO

BACKGROUND: On January 12, 2010, Haiti experienced the western hemisphere's worst-ever natural disaster. Within 24 hours, the United States Naval Ship Comfort received orders to respond, and a group of more than 500 physicians, nurses, and staff undertook the largest and most rapid triage and treatment since the inception of hospital ships. METHODS: These data represent pediatric surgical patients treated aboard the United States Naval Ship Comfort between January 19 and February 27, 2010. Prospective databases managed by patient administration, radiology, blood bank, laboratory services, and surgical services were combined to create an overall patient care database that was retrospectively reviewed for this analysis. RESULTS: Two hundred thirty-seven pediatric surgical patients were treated, representing 27% of the total patient population. These patients underwent a total of 213 operations composed of 243 unique procedures. Orthopedic procedures represented 71% of the total caseload. Patients returned to the operating room up to 11 times and required up to 28 days for completion of surgical management. CONCLUSIONS: This represents the largest cohort of pediatric surgical patients in an earthquake response. Our analysis provides a model for anticipating surgical caseload, injury patterns, and duration of surgical course in preparing for future disaster response missions. Moreover, we propose a 3-phased response to disaster medicine that has not been previously described.


Assuntos
Medicina de Desastres/organização & administração , Terremotos , Cirurgia Geral/organização & administração , Hospitais Militares/organização & administração , Missões Médicas/organização & administração , Modelos Teóricos , Medicina Naval/organização & administração , Pediatria/organização & administração , Navios , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , Queimaduras/epidemiologia , Queimaduras/cirurgia , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Grupos Diagnósticos Relacionados , Planejamento em Desastres , Feminino , Haiti , Número de Leitos em Hospital , Humanos , Lactente , Masculino , Triagem , Estados Unidos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/cirurgia
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