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1.
PLOS Digit Health ; 2(5): e0000237, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37205713

RESUMO

Artificial intelligence (AI) has the potential to improve diagnostic accuracy. Yet people are often reluctant to trust automated systems, and some patient populations may be particularly distrusting. We sought to determine how diverse patient populations feel about the use of AI diagnostic tools, and whether framing and informing the choice affects uptake. To construct and pretest our materials, we conducted structured interviews with a diverse set of actual patients. We then conducted a pre-registered (osf.io/9y26x), randomized, blinded survey experiment in factorial design. A survey firm provided n = 2675 responses, oversampling minoritized populations. Clinical vignettes were randomly manipulated in eight variables with two levels each: disease severity (leukemia versus sleep apnea), whether AI is proven more accurate than human specialists, whether the AI clinic is personalized to the patient through listening and/or tailoring, whether the AI clinic avoids racial and/or financial biases, whether the Primary Care Physician (PCP) promises to explain and incorporate the advice, and whether the PCP nudges the patient towards AI as the established, recommended, and easy choice. Our main outcome measure was selection of AI clinic or human physician specialist clinic (binary, "AI uptake"). We found that with weighting representative to the U.S. population, respondents were almost evenly split (52.9% chose human doctor and 47.1% chose AI clinic). In unweighted experimental contrasts of respondents who met pre-registered criteria for engagement, a PCP's explanation that AI has proven superior accuracy increased uptake (OR = 1.48, CI 1.24-1.77, p < .001), as did a PCP's nudge towards AI as the established choice (OR = 1.25, CI: 1.05-1.50, p = .013), as did reassurance that the AI clinic had trained counselors to listen to the patient's unique perspectives (OR = 1.27, CI: 1.07-1.52, p = .008). Disease severity (leukemia versus sleep apnea) and other manipulations did not affect AI uptake significantly. Compared to White respondents, Black respondents selected AI less often (OR = .73, CI: .55-.96, p = .023) and Native Americans selected it more often (OR: 1.37, CI: 1.01-1.87, p = .041). Older respondents were less likely to choose AI (OR: .99, CI: .987-.999, p = .03), as were those who identified as politically conservative (OR: .65, CI: .52-.81, p < .001) or viewed religion as important (OR: .64, CI: .52-.77, p < .001). For each unit increase in education, the odds are 1.10 greater for selecting an AI provider (OR: 1.10, CI: 1.03-1.18, p = .004). While many patients appear resistant to the use of AI, accuracy information, nudges and a listening patient experience may help increase acceptance. To ensure that the benefits of AI are secured in clinical practice, future research on best methods of physician incorporation and patient decision making is required.

2.
Ann Thorac Surg ; 114(1): 61-68, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35189111

RESUMO

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.


Assuntos
COVID-19 , Coronavirus , Oxigenação por Membrana Extracorpórea , Adulto , Teorema de Bayes , COVID-19/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Ann Thorac Surg ; 113(5): 1452-1460, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34242641

RESUMO

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in the management of patients with COVID-19 continues to evolve. The purpose of this analysis is to review our multi-institutional clinical experience involving 200 consecutive patients at 29 hospitals with confirmed COVID-19 supported with ECMO. METHODS: This analysis includes our first 200 COVID-19 patients with complete data who were supported with and separated from ECMO. These patients were cannulated between March 17 and December 1, 2020. Differences by mortality group were assessed using χ2 tests for categoric variables and Kruskal-Wallis rank sum tests and Welch's analysis of variance for continuous variables. RESULTS: Median ECMO time was 15 days (interquartile range, 9 to 28). All 200 patients have separated from ECMO: 90 patients (45%) survived and 110 patients (55%) died. Survival with venovenous ECMO was 87 of 188 patients (46.3%), whereas survival with venoarterial ECMO was 3 of 12 patients (25%). Of 90 survivors, 77 have been discharged from the hospital and 13 remain hospitalized at the ECMO-providing hospital. Survivors had lower median age (47 versus 56 years, P < .001) and shorter median time from diagnosis to ECMO cannulation (8 versus 12 days, P = .003). For the 90 survivors, adjunctive therapies on ECMO included intravenous steroids (64), remdesivir (49), convalescent plasma (43), anti-interleukin-6 receptor blockers (39), prostaglandin (33), and hydroxychloroquine (22). CONCLUSIONS: Extracorporeal membrane oxygenation facilitates survival of select critically ill patients with COVID-19. Survivors tend to be younger and have a shorter duration from diagnosis to cannulation. Substantial variation exists in drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , COVID-19/terapia , Estado Terminal , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Imunização Passiva , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Soroterapia para COVID-19
5.
Thromb Res ; 204: 66-75, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34147831

RESUMO

BACKGROUND: Patients' responses to antiplatelet therapy significantly vary, with individuals showing high residual platelet reactivity associated with thrombosis. To personalize thrombosis management, platelet function testing has been suggested as a promising tool able to monitor the antithrombotic effect of antiplatelet agents in real-time. We have prototyped the MICELI, a miniature and easy-to-use electrical impedance aggregometer (EIA), measuring platelet aggregation in whole blood. Here, we tested the capability of the MICELI aggregometer to quantify platelet reactivity on antiplatelet agents, as compared with conventional light-transmission aggregometry (LTA). METHODS: Platelet aggregation in ACD-anticoagulated whole blood and platelet-rich plasma of healthy donors (n = 30) was evaluated. The effect of clopidogrel, ticagrelor, cangrelor, cilostazol, and tirofiban on ADP-induced aggregation was tested, while aspirin was evaluated with arachidonic acid and collagen. Platelet aggregation was recorded using the MICELI or BioData PAP-8E (Bio/Data Corp.) aggregometers. RESULTS: The MICELI aggregometer detected an adequate and comparable dose-dependent decrease of platelet aggregation in response to increments of drugs' concentrations, as compared to LTA (the inter-device R2 = 0.79-0.93). Platelet aggregation in platelet-rich plasma recorded by LTA showed higher sensitivity to antiplatelet agents, but it couldn't distinguish between different drug doses as indicated by saturation of the aggregatory response. CONCLUSION: Platelet aggregation in whole blood as recorded by EIA represents a better model system for evaluation of platelet reactivity as compared with platelet aggregation in platelet-rich plasma as recorded by LTA, since EIA takes into consideration the modulatory effect of other blood cells on platelet hemostatic function and pharmacodynamics of antiplatelet drugs in vivo. As such, the MICELI impedance aggregometer could be potentially employed for the point-of-care monitoring of platelet function in patients on-treatment for personalized tailoring of their antiplatelet regimen.


Assuntos
Inibidores da Agregação Plaquetária , Testes de Função Plaquetária , Plaquetas , Impedância Elétrica , Humanos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia
6.
ASAIO J ; 67(10): 1087-1096, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34191753

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.


Assuntos
Injúria Renal Aguda , COVID-19/complicações , Rim/patologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , COVID-19/patologia , Humanos , Necrose Tubular Aguda/patologia , SARS-CoV-2
8.
J Pain ; 22(7): 763-777, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33636371

RESUMO

A growing body of evidence supports the modulation of pain by light exposure. As such, phototherapy is being increasingly utilized for the management of a variety of pain conditions. The modes of delivery, and hence applications of phototherapy, vary by wavelength, intensity, and route of exposure. As such, differing mechanisms of action exist depending upon those parameters. Cutaneous application of red light (660 nm) has been shown to reduce pain in neuropathies and complex regional pain syndrome-I, whereas visual application of the same wavelength of red light has been reported to exacerbate migraine headache in patients and lead to the development of functional pain in animal models. Interestingly visual exposure to green light can result in reduction in pain in variety of pain conditions such as migraine and fibromyalgia. Cutaneous application typically requires exposure on the order of minutes, whereas visual application requires exposure on the order of hours. Both routes of exposure elicit changes centrally in the brainstem and spinal cord, and peripherally in the dorsal root ganglia and nociceptors. The mechanisms of photobiomodulation of pain presented in this review provide a foundation in furtherance of exploration of the utility of phototherapy as a tool in the management of pain. PERSPECTIVE: This review synopsizes the pathways and mechanisms through which light modulates pain and the therapeutic utility of different colors and exposure modalities of light on pain. Recent advances in photobiomodulation provide a foundation for understanding this novel treatment for pain on which future translational and clinical studies can build upon.


Assuntos
Manejo da Dor , Dor/etiologia , Fototerapia , Humanos , Transdução de Sinal Luminoso/fisiologia , Vias Neurais/fisiologia , Dor/fisiopatologia , Dor/psicologia
9.
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
10.
ASAIO J ; 66(2): 190-198, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30845067

RESUMO

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for the unmet clinical need of inoperable patients with severe aortic stenosis (AS). Current clinically used tissue TAVR valves suffer from limited durability that hampers TAVR's rapid expansion to younger, lower risk patients. Polymeric TAVR valves optimized for hemodynamic performance, hemocompatibility, extended durability, and resistance to calcific degeneration offer a viable solution to this challenge. We present extensive in vitro durability and stability testing of a novel polymeric TAVR valve (PolyNova valve) using 1) accelerated wear testing (AWT, ISO 5840); 2) calcification susceptibility (in the AWT)-compared with clinically used tissue valves; and 3) extended crimping stability (valves crimped to 16 Fr for 8 days). Hydrodynamic testing was performed every 50M cycles. The valves were also evaluated visually for structural integrity and by scanning electron microscopy for evaluation of surface damage in the micro-scale. Calcium and phosphorus deposition was evaluated using micro-computed tomography (µCT) and inductive coupled plasma spectroscopy. The valves passed 400M cycles in the AWT without failure. The effective orifice area kept stable at 1.8 cm with a desired gradual decrease in transvalvular pressure gradient and regurgitation (10.4 mm Hg and 6.9%, respectively). Calcium and phosphorus deposition was significantly lower in the polymeric valve: down by a factor of 85 and 16, respectively-as compared to a tissue valve. Following the extended crimping testing, no tears nor surface damage were evident. The results of this study demonstrate the potential of a polymeric TAVR valve to be a viable alternative to tissue-based TAVR valves.


Assuntos
Próteses Valvulares Cardíacas , Teste de Materiais , Estirenos , Estenose da Valva Aórtica/cirurgia , Calcinose/etiologia , Próteses Valvulares Cardíacas/efeitos adversos , Hemodinâmica , Humanos , Técnicas In Vitro , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/métodos
11.
J Heart Lung Transplant ; 38(6): 658-667, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30846234

RESUMO

BACKGROUND: We systematically analyzed the synergistic effect of: (i) cytokine-mediated inflammatory activation of endothelial cells (ECs) with and (ii) shear-mediated platelet activation (SMPA) as a potential contributory mechanism to intraventricular thrombus formation in the setting of left ventricular assist device (LVAD) support. METHODS: Intact and shear-activated human platelets were exposed to non-activated and cytokine-activated ECs. To modulate the level of LVAD-related shear activation, platelets were exposed to shear stress patterns of varying magnitude (30, 50, and 70 dynes/cm2, 10 minutes) via a hemodynamic shearing device. ECs were activated via exposure to inflammatory tumor necrosis factor-α (TNF-α 10 and 100 ng/ml, 24 hours), consistent with inflammatory activation recorded in patients on LVAD circulatory support. RESULTS: Adhesivity of shear-activated platelets to ECs was significantly higher than that of intact/unactivated platelets, regardless of the initial activation level (70 dynes/cm2 shear-activated platelets vs intact platelets: +80%, p < 0.001). Importantly, inflammatory activation of ECs amplified platelet prothrombinase activity progressively with increasing shear stress magnitude and TNF-α concentration: thrombin generation of 70 dynes/cm2 shear-activated platelets was 2.6-fold higher after exposure and adhesion to 100 ng/ml TNF-α‒activated ECs (p < 0.0001). CONCLUSIONS: We demonstrated synergistic effect of SMPA and cytokine-mediated EC inflammatory activation to enhance EC‒platelet adhesion and platelet prothrombotic function. These mechanisms may contribute to intraventricular thrombosis in the setting of mechanical circulatory support.


Assuntos
Células Endoteliais/fisiologia , Coração Auxiliar , Ativação Plaquetária/fisiologia , Trombose/etiologia , Fator de Necrose Tumoral alfa/farmacologia , Técnicas de Cultura de Células , Células Endoteliais/efeitos dos fármacos , Humanos , Ativação Plaquetária/efeitos dos fármacos , Resistência ao Cisalhamento , Estresse Mecânico
12.
J Clin Med ; 8(2)2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720769

RESUMO

Tissue engineering has gained attention as an alternative approach for developing small diameter tissue-engineered vascular grafts intended for bypass surgery, as an option to treat coronary heart disease. To promote the formation of a healthy endothelial cell monolayer in the lumen of the graft, polycaprolactone/gelatin/fibrinogen scaffolds were developed, and the surface was modified using thermoforming and coating with collagen IV and fibronectin. Human cord blood-derived endothelial cells (hCB-ECs) were seeded onto the scaffolds and the important characteristics of a healthy endothelial cell layer were evaluated under static conditions using human umbilical vein endothelial cells as a control. We found that polycaprolactone/gelatin/fibrinogen scaffolds that were thermoformed and coated are the most suitable for endothelial cell growth. hCB-ECs can proliferate, produce endothelial nitric oxide synthase, respond to interleukin 1 beta, and reduce platelet deposition.

13.
ACS Biomater Sci Eng ; 5(8): 3864-3875, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-33438426

RESUMO

Collective cell migration is vital to tissue remodeling in wound repair, development, and cancer invasion. Nevertheless, studies on collective cell migration have largely focused on epithelial growth and repair mechanisms and have only recently expanded to explore coordinated metastatic cancer and smooth muscle cell behaviors. The regulatory mechanisms of smooth muscle cell collective migration, such as leader-follower organization and mechanosensitivity, remain poorly understood. In this study, we demonstrate the involvement of leader cells during collective smooth muscle cell migration using dynamic cell tracking and single cell gene expression analysis. Engineered wound models, including ingrowth, outgrowth, and straight edge geometries, along with traction force microscopy and finite element stress mapping reveal that smooth muscle leader cells are enhanced at the wound edge when the intercellular tension near the cell wound boundary is reduced. Pharmacological perturbation further supports the notion that mechanical force negatively regulates the formation of leader cells. The mechanical regulation of collective smooth muscle cell migration via the formation of leader cells may lead to novel treatment strategies for pathogenic smooth muscle cell conditions in the future.

14.
Ann Thorac Surg ; 105(2): e47-e49, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29362190

RESUMO

In patients with left ventricular assist device support and aspirin allergy, the choice of effective antiplatelet strategy remains a challenge. We compared the antithrombotic effect of clopidogrel vs ticagrelor in an LVAD patient with aspirin allergy by using a modified protocol of the thrombin generation test, accounting selectively for the platelet contribution on thrombin generation. Our results demonstrate enhanced antithrombotic efficacy offered by ticagrelor. Consistent with experimental results, the patient has passed more than 300 days without thromboembolic complications. This study provides additional mechanistic rationale supporting clinical evidence and opens the perspective to identify individual poor responsiveness to drugs by specifically evaluating drug-mediated platelet function.


Assuntos
Aspirina/efeitos adversos , Coração Auxiliar , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Varfarina/uso terapêutico , Clopidogrel , Hipersensibilidade a Drogas , Quimioterapia Combinada , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Ticlopidina/uso terapêutico
15.
Med Eng Phys ; 48: 31-38, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28869117

RESUMO

Thrombus formation is a major adverse event affecting patients implanted with ventricular assist devices (VADs). Despite anti-thrombotic drug administration, thrombotic events remain frequent within the first year post-implantation. Platelet activation (PA) is an essential process underling thrombotic adverse events in VAD systems. Indeed, abnormal shear forces, correlating with specific flow trajectories of VADs, are strong agonists mediating PA. To date, the ability to determine efficacy of anti-platelet (AP) agents under shear stress conditions is limited. Here, we present a novel microfluidic platform designed to replicate shear stress patterns of a clinical VAD, and use it to compare the efficacy of two AP agents in vitro. Gel-filtered platelets were incubated with i) acetylsalicylic acid (ASA) and ii) ticagrelor, at two different concentrations (ASA: 125 and 250 µM; ticagrelor: 250 and 500 nM) and were circulated in the VAD-emulating microfluidic platform using a peristaltic pump. GFP was collected after 4 and 52 repetitions of exposure to the VAD shear pattern and tested for shear-mediated PA. ASA significantly inhibited PA only at 2-fold higher concentration (250 µM) than therapeutic dose (125 µM). The effect of ticagrelor was not dependent on drug concentration, and did not show significant inhibition with respect to untreated control. This study demonstrates the potential use of microfluidic platforms as means of testing platelet responsiveness and AP drug efficacy under complex and realistic VAD-like shear stress conditions.


Assuntos
Avaliação Pré-Clínica de Medicamentos/instrumentação , Coração Auxiliar , Dispositivos Lab-On-A-Chip , Inibidores da Agregação Plaquetária/farmacologia , Resistência ao Cisalhamento , Adenosina/análogos & derivados , Adenosina/farmacologia , Aspirina/farmacologia , Sonicação , Ticagrelor
16.
Artif Organs ; 40(12): E292-E304, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27911025

RESUMO

Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving and effective alternative to surgical valve replacement in high-risk, elderly patients with severe calcific aortic stenosis. Despite its early promise, certain limitations and adverse events, such as suboptimal placement and valve migration, have been reported. In the present study, it was aimed to evaluate the effect of various TAVR deployment locations on the procedural outcome by assessing the risk for valve migration. The deployment of a balloon-expandable Edwards SAPIEN valve was simulated via finite element analysis in a patient-specific calcified aortic root, which was reconstructed from CT scans of a retrospective case of valve migration. The deployment location was parametrized in three configurations and the anchorage was quantitatively assessed based on the contact between the stent and the native valve during the deployment and recoil phases. The proximal deployment led to lower contact area between the native leaflets and the stent which poses higher risk for valve migration. The distal and midway positions resulted in comparable outcomes, with the former providing a slightly better anchorage. The approach presented might be used as a predictive tool for procedural planning in order to prevent prosthesis migration and achieve better clinical outcomes.


Assuntos
Aorta/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/patologia , Calcinose/cirurgia , Falha de Prótese , Substituição da Valva Aórtica Transcateter/métodos , Idoso de 80 Anos ou mais , Aorta/anatomia & histologia , Valva Aórtica/cirurgia , Simulação por Computador , Análise de Elementos Finitos , Humanos , Masculino , Modelos Anatômicos , Modelos Biológicos , Desenho de Prótese , Estudos Retrospectivos , Resultado do Tratamento
17.
Plast Reconstr Surg Glob Open ; 4(7): e810, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27536489

RESUMO

We report on the use of free fat grafting as a means of redistributing normal and shear stress after healing of plantar diabetic foot wounds. Although fat augmentation (lipofilling) has been described previously as an approach to supplement defects and prevent atrophy, including use as an adjunct to wound healing and to mitigate pain in the foot, we are unaware of any reports in the medical literature that have described its use in the high-risk diabetic foot in remission. An active 37-year-old man with type 2 diabetes and neuropathy presented with gangrene of his fifth ray, which was amputated. He subsequently developed a chronic styloid process ulceration that progressed despite treatment. We performed a tibialis anterior tendon transfer and total contact casting. He went on to heal but with residual fat pad atrophy and recalcitrant preulcerative lesions. We then used autologous fat grafting for the plantar atrophy. The patient was able to successfully transition to normal shoe gear after 4 weeks with successful engraftment without complication or recurrence of the wound at 6 weeks. This therapy may provide a promising adjunct to increase ulcer-free days to the patient in diabetic foot remission.

18.
J Biomech ; 48(13): 3641-9, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26329461

RESUMO

Surgical valve replacement in patients with severe calcific aortic valve disease using either bioprosthetic or mechanical heart valves is still limited by structural valve deterioration for the former and thrombosis risk mandating anticoagulant therapy for the latter. Prosthetic polymeric heart valves have the potential to overcome the inherent material and design limitations of these valves, but their development is still ongoing. The aim of this study was to characterize the hemodynamics and thrombogenic potential of the Polynova polymeric trileaflet valve prototype using a fluid-structure interaction (FSI) approach. The FSI model replicated experimental conditions of the valve as tested in a left heart simulator. Hemodynamic parameters (transvalvular pressure gradient, flow rate, maximum velocity, and effective orifice area) were compared to assess the validity of the FSI model. The thrombogenic footprint of the polymeric valve was evaluated using a Lagrangian approach to calculate the stress accumulation (SA) values along multiple platelet trajectories and their statistical distribution. In the commissural regions, platelets were exposed to the highest SA values because of highest stress levels combined with local reverse flow patterns and vortices. Stress-loading waveforms from representative trajectories in regions of interest were emulated in our hemodynamic shearing device (HSD). Platelet activity was measured using our platelet activation state (PAS) assay and the results confirmed the higher thrombogenic potential of the commissural hotspots. In conclusion, the proposed method provides an in depth analysis of the hemodynamic and thrombogenic performance of the polymer valve prototype and identifies locations for further design optimization.


Assuntos
Valva Aórtica , Próteses Valvulares Cardíacas , Hemodinâmica , Modelos Teóricos , Ativação Plaquetária , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Plaquetas , Calcinose/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Polímeros , Desenho de Prótese , Trombose/etiologia
19.
ASAIO J ; 61(6): e44-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25914953

RESUMO

Left ventricular assist devices (LVADs) are commonly used as either a bridge-to-transplant or a destination therapy. The traditional approach for LVAD implantation is via median sternotomy, but many candidates for this procedure have a history of failed cardiac surgeries and previous sternotomy. Redo sternotomy increases the risk of heart surgery, particularly in the setting of advanced heart failure. Robotics facilitates a less invasive approach to LVAD implantation that circumvents some of the morbidity associated with a redo sternotomy. We compared the outcomes of all patients at our institution who underwent LVAD implantation via either a traditional sternotomy or using robotic assistance. The robotic cohort showed reduced resource utilization including length of hospital stay and use of blood products. As the appropriate candidates become elucidated, robotic assistance may improve the safety and cost-effectiveness of reoperative LVAD surgery.


Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Implantação de Prótese , Procedimentos Cirúrgicos Robóticos , Toracotomia , Feminino , Humanos , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Reoperação , Esternotomia , Toracotomia/métodos
20.
Artigo em Inglês | MEDLINE | ID: mdl-26736255

RESUMO

Calcific aortic valve disease (CAVD) is a cardiovascular condition that causes the progressive narrowing of the aortic valve (AV) opening, due to the growth of bone-like deposits all over the aortic root (AR). Transcatheter aortic valve replacement (TAVR), a minimally invasive procedure, has recently become the only lifesaving solution for patients that cannot tolerate the standard surgical valve replacement. However, adverse effects, such as AR injury or paravalvular leakage (PVL), may occur as a consequence of a sub-optimal procedure, due to the presence of calcifications in situ. Additionally, the crimping required for delivering the valve via stenting may damage the valve. The aim of the present study is to comparatively assess the crimping mechanics of the commercialized Edwards SAPIEN valve and an alternative polymeric valve (Polynova, Inc) and to evaluate the effect of different TAVR deployment positions using patient-specific numerical models. The optimal deployment location for achieving better patient outcomes was calculated and based on the interactions between the TAVR stent and the native AR. Results demonstrated that the Polynova valve withstands the crimping process better than the SAPIEN valve. Furthermore, deployment simulations showed the role that calcifications deposits may play in the TAVR sub-optimal valve anchoring to the AV wall, leading to the presence of gaps that result in PVL.


Assuntos
Aorta/cirurgia , Posicionamento do Paciente , Substituição da Valva Aórtica Transcateter , Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Calcinose/terapia , Análise de Elementos Finitos , Próteses Valvulares Cardíacas , Humanos , Modelos Biológicos , Stents
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