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1.
Skeletal Radiol ; 52(6): 1137-1157, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36547677

RESUMO

OBJECTIVE: To describe the ultrasound (US) appearance of regenerative peripheral nerve interfaces (RPNIs) in humans, and correlate clinically and with histologic findings from rat RPNI. MATERIALS AND METHODS: Patients (≥ 18 years) who had undergone RPNI surgery within our institution between the dates of 3/2018 and 9/2019 were reviewed. A total of 21 patients (15 male, 6 female, age 21-82 years) with technically adequate US studies of RPNIs were reviewed. Clinical notes were reviewed for the presence of persistent pain after RPNI surgery. Histologic specimens of RPNIs in a rat model from prior studies were compared with the US findings noted in this study. RESULTS: There was a variable appearance to the RPNIs including focal changes involving the distal nerve, nerve-muscle graft junction, and area of the distal sutures. The muscle grafts varied in thickness with accompanying variable echogenic changes. No interval change was noted on follow-up US studies. Diffuse hypoechoic swelling with loss of the fascicular structure of the nerve within the RPNI and focal hypoechoic changes at the nerve-muscle graft junction were associated with clinical outcomes. US findings corresponded to histologic findings in the rat RPNI. CONCLUSION: Ultrasound imaging can demonstrate various morphologic changes involving the nerve, muscle, and interface between these two biological components of RPNIs. These changes correspond to expected degenerative and regenerative processes following nerve resection and muscle reinnervation and should not be misconstrued as pathologic in all cases. N5 and N1 morphologic type changes of the RPNI were found to be associated with symptoms.


Assuntos
Regeneração Nervosa , Nervos Periféricos , Humanos , Ratos , Masculino , Feminino , Animais , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Nervos Periféricos/diagnóstico por imagem , Regeneração Nervosa/fisiologia , Músculos , Dor , Ultrassonografia
2.
Ann Surg Oncol ; 29(1): 535-544, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34480284

RESUMO

BACKGROUND: Despite awareness regarding financial toxicity in breast cancer care, little is known about the financial strain associated with breast reconstruction. This study aims to describe financial toxicity and identify factors independently associated with financial toxicity for women pursuing post-mastectomy breast reconstruction. METHODS: A 33-item electronic survey was distributed to members of the Love Research Army. Women over 18 years of age and at least 1 year after post-mastectomy breast reconstruction were invited to participate. The primary outcome of interest was self-reported financial toxicity due to breast reconstruction, while secondary outcomes of interest were patient-reported out-of-pocket expenses and impact of financial toxicity on surgical decision making. RESULTS: In total, 922 women were included (mean age 58.6 years, standard deviation 10.3 years); 216 women (23.8%) reported financial toxicity from reconstruction. These women had significantly greater out-of-pocket medical expenses. When compared with women who did not experience financial toxicity, those who did were more likely to have debt due to reconstruction (50.9% vs. 3.2%, p < 0.001). Younger age, lower annual household income, greater out-of-pocket expenses, and a postoperative major complication were independently associated with an increased risk for financial toxicity. If faced with the same decision, women experiencing financial toxicity were more likely to decide against reconstruction (p < 0.001) compared with women not experiencing financial toxicity. CONCLUSIONS: Nearly one in four women experienced financial toxicity from breast reconstruction. Women who reported higher levels of financial toxicity were more likely to change their decisions about surgery. Identified factors predictive of financial toxicity could guide preoperative discussions to inform decision making that mitigates undesired financial decline.


Assuntos
Neoplasias da Mama , Mamoplastia , Adolescente , Adulto , Neoplasias da Mama/cirurgia , Feminino , Estresse Financeiro , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
3.
Dis Colon Rectum ; 64(4): 429-437, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395136

RESUMO

BACKGROUND: Patients with symptomatic Crohn's disease who undergo abdominoperineal resection can experience impaired postoperative wound healing. This results in significant morbidity, burdensome dressing changes, and increased postoperative pain. When abdominoperineal resection is performed for oncological reasons, autologous flap reconstruction is occasionally performed to optimize wound healing and reconstruction outcomes. However, the role of flap reconstruction after abdominoperineal resection for Crohn's disease has not been established. OBJECTIVE: This study examines the utility of flap reconstruction in patients with symptomatic Crohn's disease undergoing abdominoperineal resection. We hypothesize that patients with immediate flap reconstruction after abdominoperineal resection will demonstrate improved wound healing. DESIGN: This study is a retrospective chart review. SETTINGS: Eligible patients at our institution were identified from 2010 to 2018 by using a combination of Current Procedural Terminology, International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision codes. PATIENTS: Of 40 adult patients diagnosed with Crohn's disease, 20 underwent abdominoperineal resection only and 20 underwent abdominoperineal resection with flap reconstruction. INTERVENTIONS: Immediate autologous flap reconstruction was performed after abdominoperineal resection. MAIN OUTCOME MEASURES: The primary outcomes measured were the presence of postoperative perineal wounds and postoperative wound care burden. RESULTS: Patients in the abdominoperineal resection with flap reconstruction group demonstrated significantly worse preoperative disease traits, including fistula burden, than patients in the abdominoperineal resection only group. A lower number of patients tended to be associated with a persistent perineal wound in the flap group at 30 days (abdominoperineal resection with flap reconstruction = 55% vs abdominoperineal resection only = 70%; p = 0.327) and at 6 months (abdominoperineal resection with flap reconstruction = 25% vs abdominoperineal resection only = 40%; p = 0.311) postoperatively. There was also a trend toward a lower incidence of complications in the flap group. Patients in the abdominoperineal resection with flap reconstruction group tended to experience lower postoperative pain than patients in the abdominoperineal resection only group. LIMITATIONS: This retrospective cohort study was limited by its reliance on data in electronic medical records, and by its small sample size and the fact that it was a single-institution study. CONCLUSIONS: In select patients who have severe perianal fistulizing Crohn's disease, there may be a benefit to immediate flap reconstruction after abdominoperineal resection to lower postoperative wound care burden without significant intraoperative or postoperative risk. In addition, flap reconstruction may lead to lower postoperative pain. See Video Abstract at http://links.lww.com/DCR/B416. EL ROL DE LA RECONSTRUCCIN CON COLGAJO AUTLOGO EN PACIENTES CON ENFERMEDAD DE CROHN SOMETIDOS A RESECCIN ABDOMINOPERINEAL: ANTECEDENTES:Los pacientes con enfermedad de Crohn sintomática que se someten a una resección abdominoperineal pueden experimentar una curación posoperatoria deficiente de la herida. Esto da como resultado una morbilidad significativa, cambios de apósito molestos y un aumento del dolor posoperatorio. Cuando se realiza una resección abdominoperineal por razones oncológicas, ocasionalmente se realiza una reconstrucción con colgajo autólogo para optimizar los resultados de la curación y reconstrucción de la herida. Sin embargo, no se ha establecido la función de la reconstrucción con colgajo después de la resección abdominoperineal para la enfermedad de Crohn.OBJETIVO:Este estudio examina la utilidad de la reconstrucción con colgajo en pacientes con enfermedad de Crohn sintomática sometidos a resección abdominoperineal. Presumimos que los pacientes con reconstrucción inmediata con colgajo después de la resección abdominoperineal demostrarán una mejor curación de la herida.DISEÑO:Revisión retrospectiva de expedientes.MARCO:Los pacientes elegibles en nuestra institución se identificaron entre 2010 y 2018 mediante una combinación de los códigos de Terminología actual de procedimientos, Clasificación internacional de enfermedades 9 y Clasificación internacional de enfermedades 10.PACIENTES:Cuarenta pacientes adultos diagnosticados con enfermedad de Crohn que se someten a resección abdominoperineal solamente (APR-solo = 20) y resección abdominoperineal con reconstrucción con colgajo (APR-colgajo = 20).INTERVENCIÓN (ES):Reconstrucción inmediata con colgajo autólogo después de la resección abdominoperineal.MEDIDAS DE RESULTADOS PRINCIPALES:Presencia de herida perineal posoperatoria y carga de cuidado de la herida posoperatoria.RESULTADOS:Los pacientes del grupo APR-colgajo demostraron rasgos de enfermedad preoperatoria significativamente peores, incluida la carga de la fístula, en comparación con los pacientes del grupo APR-solo. Un número menor de pacientes tendió a asociarse con una herida perineal persistente en el grupo de colgajo a los 30 días (APR-colgajo = 55% vs APR-solo = 70%; p = 0.327) y 6 meses (APR-colgajo = 25% vs APR-solo = 40%; p = 0.311) postoperatoriamente. También hubo una tendencia hacia una menor incidencia de complicaciones en el grupo APR-colgajo. Los pacientes del grupo APR-colgajo tendieron a experimentar menos dolor posoperatorio en comparación con el grupo APR-solo.LIMITACIONES:Estudio de cohorte retrospectivo basado en datos de historias clínicas electrónicas. Tamaño de muestra pequeño y estudio de una sola institución.CONCLUSIONES:En pacientes seleccionados que tienen enfermedad de Crohn fistulizante perianal grave, la reconstrucción inmediata del colgajo después de la resección abdominoperineal puede beneficiar a reducir la carga posoperatoria del cuidado de la herida sin riesgo intraoperatorio o posoperatorio significativo. Además, la reconstrucción con colgajo puede resultar un dolor posoperatorio menor. Consulte Video Resumen en http://links.lww.com/DCR/B416.


Assuntos
Doença de Crohn/cirurgia , Protectomia/métodos , Retalhos Cirúrgicos/transplante , Infecção da Ferida Cirúrgica/economia , Adulto , Autoenxertos/estatística & dados numéricos , Estudos de Casos e Controles , Efeitos Psicossociais da Doença , Doença de Crohn/diagnóstico , Feminino , Humanos , Fístula Intestinal/economia , Fístula Intestinal/epidemiologia , Fístula Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Dor Pós-Operatória/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Cicatrização/fisiologia
4.
Aesthet Surg J ; 39(10): 1118-1138, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30892625

RESUMO

Surgical site infections represent one of the most common postoperative complications in patients undergoing aesthetic surgery. As with other postoperative complications, the incidence of these infections may be influenced by many factors and varies depending on the specific operation performed. Understanding the risk factors for infection development is critical because careful patient selection and appropriate perioperative counseling will set the right expectations and can ultimately improve patient outcomes and satisfaction. Various perioperative prevention measures may also be employed to minimize the incidence of these infections. Once the infection occurs, prompt diagnosis will allow management of the infection and any associated complications in a timely manner to ensure patient safety, optimize the postoperative course, and avoid long-term sequelae.


Assuntos
Técnicas Cosméticas/efeitos adversos , Assistência Perioperatória/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Humanos , Incidência , Fatores de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle
5.
Aesthet Surg J ; 39(1): 109-119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29659716

RESUMO

Background: Smoking has been associated with several postoperative adverse outcomes across multiple surgical disciplines, but the literature is limited for aesthetic surgical procedures. Objectives: To compare complication rates between smokers and nonsmokers undergoing common cosmetic procedures, identify specific cosmetic procedures where smoking increases the risk of complications, and evaluate smoking as an independent risk factor for major complications following aesthetic surgery. Methods: A prospective cohort of patients undergoing cosmetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Smoking was evaluated as a risk factor for major complications requiring emergency room visit, hospital admission, or reoperation within 30 days after surgery. Multivariate regression analysis was performed controlling for the effects of age, gender, body mass index, type of surgical facility, type of procedure, and combined procedures. Results: Of the 129,007 patients, 10,621 (8.2%) were smokers. All procedures examined, except breast augmentation, were more frequently performed in the nonsmoker cohort. Overall major complications were similar between smokers and nonsmokers (2.0% vs 1.9%, P = 0.57). In univariate analysis, surgical site infections (0.6% vs 0.5%, P = 0.04) were significantly higher among smokers, but suspected venous thromboembolism (0.2% vs 0.1%, P = 0.01) was significantly higher among nonsmokers. Notably, smokers had a higher risk of major complications after body procedures (2.9% vs 1.0%, P = 0.01), as well as thigh lifts (23.8% vs 3.6%, P < 0.01) and male breast surgery (3.7% vs 1.4%, P = 0.03). In multivariate analysis, smoking was found to be an independent predictor of surgical site infections (relative risk 1.61, P < 0.01). Conclusions: Smoking is an independent risk factor of major surgical site infections following aesthetic surgery. Body procedures, as well as thigh lifts and male breast surgery, have higher complication rates in smokers.


Assuntos
Procedimentos de Cirurgia Plástica/efeitos adversos , Fumar/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Fatores Etários , Índice de Massa Corporal , Conjuntos de Dados como Assunto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/cirurgia
9.
Aesthet Surg J ; 38(9): 1013-1025, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-29474524

RESUMO

Hematomas represent one of the most common postoperative complications in patients undergoing aesthetic surgery. Depending on the type of procedure performed, hematoma incidence and presentation can vary greatly. Understanding the risk factors for hematoma formation and the preoperative considerations to mitigate the risk is critical to provide optimal care to the aesthetic patient. Various perioperative prevention measures may also be employed to minimize hematoma incidence. The surgeon's ability to adequately diagnose and treat hematomas after aesthetic surgery is not only crucial to patient care but also minimizes the risk of further complications or long-term sequelae. Understanding hematoma development and management enhances patient safety and will lead to overall increased patient satisfaction after aesthetic surgery.


Assuntos
Hematoma/epidemiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Estética , Feminino , Hematoma/diagnóstico , Hematoma/etiologia , Hematoma/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco , Fatores Sexuais
11.
Aesthet Surg J ; 37(7): 757-767, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28472446

RESUMO

Background: Rhinoplasty remains one of the most common aesthetic procedures performed in the United States. Current literature on rhinoplasty complications is inconclusive and is based on retrospective reviews and small cohorts. Objectives: The purpose of this study was to examine the incidence and identify predictive risk factors for major complications following rhinoplasty alone or in combination with other aesthetic operations in a large, prospective, multicenter database study. Methods: A prospective cohort of patients undergoing rhinoplasty between May 2008 and May 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications, defined as complications requiring an emergency room visit, hospital admission, or a reoperation within 30 days of the index operation. Univariate and multivariate analysis evaluated potential risk factors for major complications including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, and combined procedures. Results: A total of 129,007 patients were identified, of which 4978 (3.9%) underwent a rhinoplasty. The overall complication rate was 0.7% (n = 37). Hematoma was the most common complication (0.2%), followed by infection (0.2%), and pulmonary complications (0.1%). Age ≥40 years was found to be an independent risk factor for developing complications. Age ≥40 years was found to have a relative risk of 2.05 (P = 0.04) for any major complication. Complications increased from 0.58% in rhinoplasty alone cases to 1.02% (P < 0.05) with the addition of 1 other body region to 2.09% with the addition of 2 other body regions (P < 0.05). The risk of pulmonary complications increased from 0.1% to 1% (P < 0.05) with the addition of rhinoplasty with 2 other body regions. Gender, type of facility, smoking status, and BMI ≥25 did not appear to significantly impact the risk for major complications. Conclusions: The major complication rate following rhinoplasty remains low. The risk is increased with age ≥40 years and with the addition of other cosmetic procedures. Pulmonary complications, although rare, do occur, and also increase when combining rhinoplasty with other aesthetic surgery. These findings are important to consider when planning rhinoplasty and educating patients on the safety of combined aesthetic surgeries. Level of Evidence: 2.


Assuntos
Estética , Pneumopatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Rinoplastia/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Reoperação/estatística & dados numéricos , Rinoplastia/métodos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
12.
Aesthet Surg J ; 37(10): 1175-1185, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-28398469

RESUMO

BACKGROUND: Postoperative hematomas are one of the most frequent complications following aesthetic surgery. Identifying risk factors for hematoma has been limited by underpowered studies from single institution experiences. OBJECTIVES: To examine the incidence and identify independent risk factors for postoperative hematomas following cosmetic surgery utilizing a prospective, multicenter database. METHODS: A prospectively enrolled cohort of patients who underwent aesthetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major hematomas requiring emergency room visit, hospital admission, or reoperation within 30 days of the index operation. Univariate and multivariate analysis was used to identify potential risk factors for hematomas including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, procedure by body region, and combined procedures. RESULTS: Of 129,007 patients, 1180 (0.91%) had a major hematoma. Mean age (42.0 ± 13.0 years vs 40.9 ± 13.9 years, P < 0.01) and BMI (24.5 ± 5.0 kg/m2 vs 24.3 ± 4.6 kg/m2, P < 0.01) were higher in patients with hematomas. Males suffered more hematomas than females (1.4% vs 0.9%, P < 0.01). Hematoma rates were higher in patients undergoing combined procedures compared to single procedures (1.1% vs 0.8%, P < 0.01), and breast procedures compared to body/extremity or face procedures (1.0% vs 0.8% vs 0.7%, P < 0.01). On multivariate analysis, independent predictors of hematoma included age (Relative Risk [RR] 1.01), male gender (RR 1.98), the procedure being performed in a hospital setting rather than an office-based setting (RR 1.68), combined procedures (RR 1.35), and breast procedures rather than the body/extremity and face procedures (RR 1.81). CONCLUSIONS: Major hematoma is the most common complication following aesthetic surgery. Male patients and those undergoing breast or combined procedures have a significantly higher risk of developing hematomas. LEVEL OF EVIDENCE: 2.


Assuntos
Hematoma/epidemiologia , Hospitalização/estatística & dados numéricos , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hematoma/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
14.
Cerebrovasc Dis ; 42(3-4): 263-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27173669

RESUMO

BACKGROUND: Cerebral vasospasm and sodium and fluid imbalances are common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and cause of significant morbidity and mortality. Studies have shown the benefit of corticosteroids in the management of these sequelae. We have reviewed the literature and analyzed the available data for corticosteroid use after SAH. METHODS: PubMed, EMBASE, and Cochrane electronic databases were searched without language restrictions, and 7 observational, controlled clinical studies of the effect of corticosteroids in the management of SAH patients were identified. Data on sodium and fluid balances, symptomatic vasospasm (SVS), and outcomes were pooled for meta-analyses using the Mantel-Haenszel random effects model. RESULTS: Corticosteroids, specifically hydrocortisone and fludrocortisone, decreased natriuretic diuresis and incidence of hypovolemia. Corticosteroid administration is associated with lower incidence of SVS in the absence of nimodipine, but does not alter the neurological outcome. CONCLUSIONS: Supplementation of corticosteroids with mineralocorticoid activity, such as hydrocortisone or fludrocortisone, helps in maintaining sodium and volume homeostasis in SAH patients. Larger trials are warranted to confirm the effects of corticosteroids on SVS and patient outcomes.


Assuntos
Corticosteroides/uso terapêutico , Hidrocortisona/uso terapêutico , Hiponatremia/tratamento farmacológico , Hipovolemia/tratamento farmacológico , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoespasmo Intracraniano/tratamento farmacológico , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/fisiopatologia , Distribuição de Qui-Quadrado , Fludrocortisona/uso terapêutico , Humanos , Hiponatremia/diagnóstico , Hiponatremia/fisiopatologia , Hipovolemia/diagnóstico , Hipovolemia/fisiopatologia , Natriurese/efeitos dos fármacos , Razão de Chances , Sódio/sangue , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos , Vasoespasmo Intracraniano/diagnóstico , Vasoespasmo Intracraniano/fisiopatologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
17.
Glia ; 62(12): 1982-91, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25042766

RESUMO

Microglia are rapidly activated in the central nervous system (CNS) in response to a variety of injuries, including inflammation, trauma, and stroke. In addition to modulation of the innate immune response, a key function of microglia is the phagocytosis of dying cells and cellular debris, which can facilitate recovery. Despite emerging evidence that axonal debris can pose a barrier to regeneration of new axons in the CNS, little is known of the cellular and molecular mechanisms that underlie clearance of degenerating CNS axons. We utilize a custom micropatterned microfluidic system that enables robust microglial-axon co-culture to explore the role of Toll-like receptors (TLRs) in microglial phagocytosis of degenerating axons. We find that pharmacologic and genetic disruption of TLR4 blocks induction of the Type-1 interferon response and inhibits phagocytosis of axon debris in vitro. Moreover, TLR4-dependent microglial clearance of unmyelinated axon debris facilitates axon outgrowth. In vivo, microglial phagocytosis of CNS axons undergoing Wallerian degeneration in a dorsal root axotomy model is impaired in adult mice in which TLR4 has been deleted. Since purinergic receptors can influence TLR4-mediated signaling, we also explored a role for the microglia P2 receptors and found that the P2X7R contributes to microglial clearance of degenerating axons. Overall, we identify TLR4 as a key player in axonal debris clearance by microglia, thus creating a more permissive environment for axonal outgrowth. Our findings have significant implications for the development of protective and regenerative strategies for the many inflammatory, traumatic, and neurodegenerative conditions characterized by CNS axon degeneration.


Assuntos
Axônios/patologia , Microglia/metabolismo , Degeneração Neural/patologia , Fagocitose/genética , Receptor 4 Toll-Like/deficiência , Animais , Antígeno CD11b/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Técnicas de Cocultura , Citocinas/metabolismo , Embrião de Mamíferos , Hipocampo/citologia , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Técnicas Analíticas Microfluídicas , Degeneração Neural/genética , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonamidas/farmacologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
18.
Semin Plast Surg ; 38(1): 39-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38495060

RESUMO

The financial burden of breast cancer treatment and reconstruction is a significant concern for patients. Patient desire for preoperative cost-of-care counseling while navigating the reconstructive process remains unknown. A cross-sectional survey of women from the Love Research Army was conducted. An electronic survey was distributed to women over 18 years of age and at least 1 year after postmastectomy breast reconstruction. Descriptive statistics and multivariable modeling were used to determine desire for and occurrence of cost-of-care discussions, and factors associated with preference for such discussions. Secondary outcomes included the association of financial toxicity with desire for cost discussions. Among 839 women who responded, 620 women (74.1%) did not speak to their plastic surgeon and 480 (57.4%) did not speak to a staff member regarding costs of breast reconstruction. Of the 550 women who reported it would have been helpful to discuss costs, 315 (57.3%) were not engaged in a financial conversation initiated by a health care provider. A greater proportion of women who reported financial toxicity, compared to those who did not, would have preferred to discuss costs with their plastic surgeon (65.2% vs. 43.5%, p < 0.001) or a staff member (75.5% vs. 59.3%, p < 0.001). Among women with financial toxicity, those who had some form of insurance (private, Medicaid, Medicare, "other") were significantly more likely to prefer a cost-of-care discussion ( p < 0.001, p = 0.02, p = 0.05, p = 0.01). Financial discussions about the potential costs of breast reconstruction seldom occurred in this national cohort. Given the reported preference and unmet need for financial discussions by a majority of women, better cost transparency and communication is needed.

19.
J Neurosci ; 32(22): 7745-57, 2012 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-22649252

RESUMO

Following CNS injury, microglial phagocytosis of damaged endogenous tissue is thought to play an important role in recovery and regeneration. Previous work has focused on delineating mechanisms of clearance of neurons and myelin. Little, however, is known of the mechanisms underlying phagocytosis of axon debris. We have developed a novel microfluidic platform that enables coculture of microglia with bundles of CNS axons to investigate mechanisms of microglial phagocytosis of axons. Using this platform, we find that axon degeneration results in the induction of type-1 interferon genes within microglia. Pharmacologic and genetic disruption of Toll/interleukin-1 receptor domain-containing adapter inducing interferon-ß (TRIF), a Toll-like receptor adapter protein, blocks induction of the interferon response and inhibits microglial phagocytosis of axon debris in vitro. In vivo, microglial phagocytosis of axons following dorsal root axotomy is impaired in mice in which TRIF has been genetically deleted. Furthermore, we identify the p38 mitogen-activated protein kinase (MAPK) cascade as a signaling pathway downstream of TRIF following axon degeneration and find that inhibition of p38 MAPK by SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole) also blocked clearance of axon debris. Finally, we find that TRIF-dependent microglial clearance of unmyelinated axon debris facilitates axon outgrowth. Overall, we provide evidence that TRIF-mediated signaling plays an unexpected role in axonal debris clearance by microglia, thereby facilitating a more permissive environment for axonal outgrowth. Our study has significant implications for the development of novel regenerative and restorative strategies for the many traumatic, neuroinflammatory, and neurodegenerative conditions characterized by CNS axon degeneration.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Interferon beta/metabolismo , Microglia/fisiologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Fagocitose/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/química , Proteínas Adaptadoras de Transporte Vesicular/deficiência , Trifosfato de Adenosina/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Axônios/patologia , Axotomia , Antígeno CD11b/metabolismo , Células Cultivadas , Quimiocina CXCL10/metabolismo , Técnicas de Cocultura , Modelos Animais de Doenças , Embrião de Mamíferos , Inibidores Enzimáticos/farmacologia , Gânglios Espinais/lesões , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipocampo/citologia , Humanos , Imidazóis/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise em Microsséries , Técnicas Analíticas Microfluídicas , Degeneração Neural/induzido quimicamente , Neurônios/citologia , Neurônios/efeitos dos fármacos , Óxido Nítrico/farmacologia , Peptídeos/farmacologia , Fagocitose/genética , Piridinas/farmacologia , Compostos de Amônio Quaternário/toxicidade , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/metabolismo , Fatores de Tempo , Transfecção
20.
Plast Reconstr Surg ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37927033

RESUMO

SUMMARY: Innovations in the fields of prosthetic devices and neuroprosthetic control strategies have opened new frontiers for the treatment and rehabilitation of individuals undergoing amputation. Commercial prosthetic devices are now available with sophisticated electrical and mechanical components that can closely replicate the functions of the human musculoskeletal system. However, to truly recognize the potential of such prosthetic devices and develop the next generation of bionic limbs, a highly reliable prosthetic device control strategy is required. In the past few years, refined surgical techniques have enabled neuroprosthetic control strategies to record efferent motor and stimulate afferent sensory action potentials from a residual limb with extraordinary specificity, signal quality, and long-term stability. As a result, such control strategies are now capable of facilitating intuitive, real-time, and naturalistic prosthetic experiences for patients with amputations. This article summarizes the current state of upper extremity neuroprosthetic devices and discusses the leading control strategies that are critical to the ongoing advancement of prosthetic development and implementation.

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