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1.
Nature ; 613(7945): 667-675, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36697864

RESUMO

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.


Assuntos
Ecocardiografia , Desenho de Equipamento , Coração , Dispositivos Eletrônicos Vestíveis , Humanos , Débito Cardíaco , Ecocardiografia/instrumentação , Ecocardiografia/normas , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Volume Sistólico , Dispositivos Eletrônicos Vestíveis/normas , Pele
2.
Artigo em Inglês | MEDLINE | ID: mdl-38890085

RESUMO

This article is the eighth in an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr Kaplan, and the editorial board for the opportunity to continue this series. In most cases, these will be research articles targeted at the perioperative echocardiographic diagnosis and treatment of patients after cardiothoracic surgery; but in some cases, the articles will target the use of perioperative echocardiography in general.

3.
J Cardiothorac Vasc Anesth ; 37(9): 1537-1549, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37208207

RESUMO

THIS SPECIAL article is part of an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the Editorial Board for the opportunity to continue this series, which focuses on the past year's research highlights that pertain to perioperative echocardiography in relation to cardiothoracic and vascular anesthesia. The major selected themes for 2022 include (1) updates on mitral valve assessments and interventions, (2) training and simulation updates, (3) outcomes and complications of transesophageal echocardiography, and (4) point-of-care cardiac ultrasound. The themes selected for this special article are just a sample of the advances in perioperative echocardiography during 2022. An appreciation and understanding of these highlights will help to ensure and improve the perioperative outcomes for patients with cardiovascular disease undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Assistência Perioperatória , Humanos , Ecocardiografia , Ecocardiografia Transesofagiana , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Valva Mitral/diagnóstico por imagem
4.
J Cardiothorac Vasc Anesth ; 36(9): 3459-3468, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680493

RESUMO

This article is the sixth of an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series. In most cases, these were research articles that were targeted at the perioperative echocardiography diagnosis and treatment of patients after cardiothoracic surgery; but, in some cases, these articles targeted the use of perioperative echocardiography in general.


Assuntos
Anestesia , Anestesiologia , Ecocardiografia , Ecocardiografia Transesofagiana , Humanos
5.
J Cardiothorac Vasc Anesth ; 36(3): 707-712, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34175203

RESUMO

OBJECTIVE: To determine if patients with congenital heart disease are undergoing laparoscopic surgery requiring abdominal insufflation and to compare the outcomes of these procedures with those who underwent an open surgical approach. DESIGN, SETTING, PARTICIPANTS: This was a retrospective study using the National Inpatient Sample from 2006 to 2014. Individuals with congenital heart disease who underwent at least one of six selected surgical procedures (laparoscopic or open) were included in the study. Subgroup analysis was performed on patients with Fontan palliation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was to determine the frequency with which congenital heart disease patients undergo laparoscopic surgery requiring abdominal insufflation compared with open surgery. Secondary outcomes included all-cause in-hospital mortality and in-hospital length of stay. Of the 5,527 patients included, nearly half underwent laparoscopic surgery (46.3%), and 128 (2.3%) had single-ventricle circulation. All-cause mortality was significantly higher for those who underwent open surgery compared with the laparoscopic approach (3.6% v 0.9%; odds ratio [OR], 4.0 [2.6-6.3]; p < 0.0001). Subgroup analysis of patients with Fontal palliation older than five years showed 30 (42%) underwent laparoscopic surgery and there was no mortality difference between the laparoscopic and open approaches (OR, 1.4 [0.2-21.3], p = 0.8). Length of stay was significantly shorter for patients undergoing laparoscopic compared with open surgery (median three days [interquartile range, two-five] v six days [three-13], p < 0.0001). CONCLUSIONS: Individuals with congenital heart disease are being offered laparoscopic surgery that requires abdominal insufflation. All-cause mortality and length of stay were higher for patients who underwent open surgical operations.


Assuntos
Cardiopatias Congênitas , Insuflação , Laparoscopia , Cardiopatias Congênitas/cirurgia , Mortalidade Hospitalar , Humanos , Tempo de Internação , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Pain Med ; 22(Suppl 1): S24-S30, 2021 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-34308955

RESUMO

Recently, basivertebral nerve (BVN) radiofrequency ablation has been developed for the treatment of chronic low back pain (CLBP) thought to arise from the vertebral body endplates (VEPs). This review describes the relevant neuroanatomy and pathobiology of VEP degeneration and injury, imaging correlates of presumed VEP pain, randomized controlled trials performed, appropriate patient selection, and safety. Anatomic, histological, and clinical evidence supports the concept of the VEP as a source of CLBP and the nociceptive role of the BVN. BVN radiofrequency ablation appears to be an effective treatment for a subset of patients with CLBP and evidence of Modic change types 1 and 2 in the L3 to S1 VEPs who have failed to respond to conservative treatment. However, all studies performed to date have been industry sponsored, and future non-industry-funded trials will be needed to confirm these results.


Assuntos
Dor Crônica , Dor Lombar , Ablação por Radiofrequência , Humanos , Dor Lombar/cirurgia , Vértebras Lombares , Imageamento por Ressonância Magnética , Resultado do Tratamento , Corpo Vertebral
7.
Anesth Analg ; 133(2): 535-552, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33755647

RESUMO

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.


Assuntos
Encefalopatias/induzido quimicamente , Encéfalo/efeitos dos fármacos , Meios de Contraste/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Manejo da Dor/efeitos adversos , Encéfalo/metabolismo , Encefalopatias/diagnóstico , Encefalopatias/metabolismo , Consenso , Meios de Contraste/administração & dosagem , Meios de Contraste/metabolismo , Técnica Delphi , Hipersensibilidade a Drogas/diagnóstico , Humanos , Dermopatia Fibrosante Nefrogênica/diagnóstico , Prognóstico , Medição de Risco , Fatores de Risco , Distribuição Tecidual
8.
J Cardiothorac Vasc Anesth ; 35(9): 2559-2568, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33934985

RESUMO

This article is the fifth of an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank Editor-in-Chief Dr. Kaplan and the editorial board for the opportunity to continue this series. In most cases, these will be research articles that are targeted at the perioperative echocardiography diagnosis and treatment of patients after cardiothoracic surgery; but in some cases, these articles will target the use of perioperative echocardiography in general.


Assuntos
Anestesia , Anestesiologia , Ecocardiografia , Ecocardiografia Transesofagiana , Humanos
9.
Pain Med ; 21(3): 570-575, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142149

RESUMO

OBJECTIVES: The S1 dorsal foramen is the route for 30% of lumbar transforaminal epidural injections; it is therefore important to identify structures impeding S1 foraminal access. The study objective was to characterize the imaging findings, prevalence, and anatomic origin of synovial cysts presenting within the S1 neural foramen. METHODS: A case series (N = 14) established imaging characteristics of S1 synovial cysts. Imaging studies of 400 patients undergoing epidural injections were reviewed for lesions compromising S1 foraminal access. Cadaveric dissections defined the relationship of the inferior recess of the L5-S1 facet to the S1 dorsal foramen. RESULTS: Elderly patients (mean age = 76) exhibited S1 synovial cysts. Synovial cysts were typically 1-2 cm in diameter, hyperintense on sagittal T2 weighted magnetic resonance images (MRIs), fluid-density on computed tomography, and dorsal to the S1 spinal nerve. Sixty percent of cysts exhibited complex MRI signal characteristics (thick wall, internal structure). Tarlov cysts, in contrast, were larger, lobular, and exhibited pure fluid intensity. Lesions impeded access to the S1 dorsal foramina in 5% of reviewed imaging studies (16 Tarlov cysts, three synovial cysts, one conjoint S1-S2 nerve root). The multifidus muscle was interposed between the L5-S1 facet inferior recess and the S1 dorsal foramen on dissection specimens; severe atrophy of the ipsilateral multifidus was noted on imaging in 17/18 synovial cysts. CONCLUSIONS: The S1 neural foramina should be inspected on sagittal MRI, when available, for confounding lesions before performing S1 epidural injections. Tarlov cysts are more common than synovial cysts; the latter are seen in elderly patients with severe multifidus atrophy.


Assuntos
Injeções Epidurais , Sacro/cirurgia , Cisto Sinovial/diagnóstico por imagem , Cisto Sinovial/epidemiologia , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Prevalência , Radiculopatia/tratamento farmacológico , Estudos Retrospectivos
10.
J Cardiothorac Vasc Anesth ; 34(8): 2036-2046, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32482504

RESUMO

This article is the fourth of an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board, for the opportunity to continue this series. In most cases, these were research articles that were targeted at the perioperative echocardiography diagnosis and treatment of patients after cardiothoracic surgery; but in some cases, these articles targetted the use of perioperative echocardiography in general.


Assuntos
Anestesia , Anestesiologia , Insuficiência da Valva Tricúspide , Ecocardiografia , Humanos
11.
J Cardiothorac Vasc Anesth ; 34(9): 2465-2475, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31587927

RESUMO

This is the final review article in a 4-part series focusing on the perioperative management of the 4 major companies' cardiovascular implantable electronic devices (CIEDs) in the United States. This article presents information pertinent to the perioperative management of Medtronic (Minneapolis, MN) transvenous CIEDs, including responses to magnet application, interpretation of interrogation reports, and basic programming (eg, mode, rate, rate modulation, and tachyarrhythmia therapies). Information regarding the Medtronic Micra (Medtronic, Minneapolis, MN) has been published previously. In addition, it contains an introduction to the concept of magnetic resonance (MR) conditional devices and magnetic resonance imaging (MRI) practices.


Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Anestesiologistas , Eletrônica , Humanos , Imageamento por Ressonância Magnética , Estados Unidos
12.
Pain Med ; 20(5): 897-906, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590777

RESUMO

OBJECTIVE: This study modeled image-guided epidural drug delivery to test whether intraprocedural distribution of pre-injected contrast reliably predicts the neuroanatomical reach of resiniferatoxin-mediated nociceptive neurolysis. METHODS: Swine (N = 12) received unilateral L4-S2 computed tomography fluoroscopy injections by a blinded neuroradiologist; 0.25 mL of contrast was pre-injected to confirm dorsal periganglionic targeting, followed by a 0.5-mL injection of 5 µg of resiniferatoxin/Tween80 or vehicle control. Epidural contrast distribution was graded according to maximum medial excursion. Spinal cord substance P immunostaining quantified the magnitude and anatomical range of resiniferatoxin activity. RESULTS: Periganglionic injection was well tolerated by all animals without development of neurological deficits or other complications. Swine were a suitable model of human clinical spinal intervention. The transforaminal approach was used at all L4 and 50% of L5 segments; the remaining segments were approached by the interlaminar route. All injections were successful with unilateral contrast distribution for all resiniferatoxin injections (N = 28). Immunohistochemistry showed bilateral ablation of substance P+ fibers entering the spinal cord of all resiniferatoxin-treated segments. The intensity of substance P immunostaining in treated segments fell below the lower 99% confidence interval of controls, defining the knockout phenotype. Substance P knockout occurred over a narrow range and was uncorrelated to the anatomical distribution of pre-injected contrast. CONCLUSIONS: Periganglionic resiniferatoxin/Tween80 induced bilateral ablation of spinal cord substance P despite exclusively unilateral targeting. These data suggest that the location of pre-injected contrast is an imperfect surrogate for the neuroanatomical range of drugs delivered to the dorsal epidural compartment that may fail to predict contralateral drug effects.


Assuntos
Diterpenos/administração & dosagem , Bloqueio Nervoso/métodos , Neurotoxinas/administração & dosagem , Animais , Feminino , Fluoroscopia/métodos , Injeções Epidurais , Raízes Nervosas Espinhais/efeitos dos fármacos , Suínos , Terapia Assistida por Computador/métodos
13.
J Cardiothorac Vasc Anesth ; 33(4): 1050-1053, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29853315

RESUMO

The management of heparin-induced thrombocytopenia (HIT) in the perioperative period for patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can be a challenging clinical scenario. Once a diagnosis of HIT has been established, heparin products typically are avoided and alternative therapies for anticoagulation are started. Alternative anticoagulation strategies for CPB are limited and often have various pharmacokinetic profiles that may lead to increased perioperative bleeding. Historically the use of a GPIIb/IIIa inhibitor, such as tirofiban, followed by unfractionated heparin (UFH) is the typical alternative for surgeries requiring DHCA in patients with HIT at the authors' institution. This article presents a case in which cangrelor followed by UFH was used in a 20-year-old patient with suspected HIT and chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy surgery requiring CPB and DHCA. Due to the frequency of significant postoperative bleeding encountered when using tirofiban and UFH, it was decided to attempt to block platelet aggregation with significantly shorter-acting cangrelor. The authors hypothesized that cangrelor would reduce the risk of significant bleeding compared with tirofiban because of its favorable pharmacokinetics. Specifically, cangrelor has a short elimination half-life of 3 to 6 minutes, and its elimination is not altered by renal and hepatic impairment. This case report discusses the pathophysiology of HIT, the alternative anticoagulants used for HIT type II in pulmonary thromboendarterectomy, and the potential of cangrelor in conjunction with UFH to be a favorable option for patients in similar clinical scenarios.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Anticoagulantes/administração & dosagem , Endarterectomia/métodos , Heparina/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Quimioterapia Combinada , Endarterectomia/efeitos adversos , Heparina/efeitos adversos , Humanos , Masculino , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto Jovem
14.
J Cardiothorac Vasc Anesth ; 33(6): 1498-1503, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30385197

RESUMO

OBJECTIVES: To assess the change in 3-dimensional (3D) echocardiography-derived right ventricular volumes before and after pulmonary thromboendarterectomy (PTE) and to evaluate the correlation of these variables with right heart catheterization-calculated pulmonary vascular resistance (PVR). SETTING: Single university hospitals. PARTICIPANTS: Patients undergoing elective PTE surgery between November 2016 and February 2018. METHODS: All patients received a pulmonary artery catheter and arterial line, and transesophageal echocardiographic monitoring was performed. Transesophageal echocardiographic monitoring before surgery (pre-PTE) and postsurgery (post-PTE) included comprehensive 2D examinations and 3D right ventricular data set acquisition for offline volumetric analysis. Right ventricular fractional area of change (RVFAC) was measured from a right ventricular-focused midesophageal 4-chamber view. TomTec-Arena 4D RV-Function 2.0 offline software (TomTec Imaging Systems GmbH, Unterschlessheim, Germany) was used to measure right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV), and right ventricular ejection fraction (RVEF). Paired t tests were used to evaluate for differences before and after surgery, and echocardiographic variables versus PVR were analyzed with linear regression. RESULTS: Forty patients were scheduled for elective PTE surgery; 35 patients had complete hemodynamic profiles and echocardiographic data sets and were included in the evaluation. Mean pulmonary artery pressure decreased from 40 ± 11 to 28 ± 7 mmHg, and PVR decreased from 708 ± 432 to 285 ± 136 dynes*s/cm5 after PTE. RVEDV decreased from 106 ± 43 to 79 ± 35 cm3 (p < 0.001), and RVESV decreased from 77 ± 36 to 59 ± 31 cm3 (p < 0.001). A statistically significant change was not identified in RVEF or RVFAC post-PTE compared with pre-PTE values. All volumetric analyses and RVFAC correlated poorly with PVR (pre-PTE RVEDV correlation to PVR [R2 = 0.004]; post-PTE RVEDV correlation to PVR [R2 = 0.024]). CONCLUSION: Even though RVEDV and RVESV displayed a statistically significant change after PTE, this study did not identify a correlation between those variables and PVR. In addition, markers of right ventricular systolic function (eg, RVFAC and RVEF) did not correlate with PVR. Therefore, the authors conclude that even though these echocardiographic measurements quantified a statistically significant change after PVR reduction, they cannot be reliably used as a surrogate marker of success immediately after PTE.


Assuntos
Volume Cardíaco , Ecocardiografia Tridimensional/métodos , Endarterectomia/métodos , Hipertensão Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico , Trombectomia/métodos , Função Ventricular Direita/fisiologia , Doença Crônica , Ecocardiografia Transesofagiana/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/cirurgia , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Pressão Propulsora Pulmonar/fisiologia
15.
J Cardiothorac Vasc Anesth ; 33(9): 2431-2444, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31076310

RESUMO

This article is the third of an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series. In most cases, these will be research articles targeted at the perioperative echocardiography diagnosis and treatment of patients after cardiothoracic surgery; but in some cases, these articles will target the use of perioperative echocardiography in general.


Assuntos
Ecocardiografia/métodos , Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Mitral/diagnóstico por imagem , Assistência Perioperatória/métodos , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Ecocardiografia/tendências , Implante de Prótese de Valva Cardíaca/tendências , Humanos , Insuficiência da Valva Mitral/cirurgia , Assistência Perioperatória/tendências , Resultado do Tratamento , Insuficiência da Valva Tricúspide/cirurgia
16.
J Cardiothorac Vasc Anesth ; 33(6): 1771-1777, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30765206

RESUMO

This article is the first in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, the associate editor-in-chief, Dr. Augoustides, and the editorial board for the opportunity to start this series, namely the research highlights of the year that pertain to electrophysiology in relation to cardiothoracic and vascular anesthesia. This first article focuses on esophageal thermal injury during radiofrequency ablation, perioperative management of patients presenting for ablation procedures, left atrial appendage occlusion devices, and, finally, heart failure diagnostic devices.


Assuntos
Anestesia/métodos , Anestesiologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Eletrofisiologia/tendências , Monitorização Fisiológica/métodos , Humanos , Monitorização Fisiológica/tendências , Publicações Periódicas como Assunto
17.
J Gene Med ; 20(7-8): e3026, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29800509

RESUMO

INTRODUCTION: Intrathecal interleukin (IL)-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, is a potential therapeutic for various human diseases, and was found to be nontoxic in dogs, when the human IL-10 ortholog was tested. However, recent studies in swine testing porcine IL-10 demonstrated fatal neurotoxicity. The present study aimed to deliver vector-encoded human IL-10 in swine, measure expression of the transgene in cerebrospinal fluid and monitor animals for signs of neurotoxicity. RESULTS: Human IL-10 levels peaked 2 weeks after vector administration followed by a rapid decline that occurred concomitant with the emergence of anti-human IL-10 antibodies in the cerebrospinal fluid and serum. Animals remained neurologically healthy throughout the study period. CONCLUSIONS: The findings of the present study suggest that swine are not idiosyncratically sensitive to intrathecal IL-10 because, recapitulating previous reports in dogs, they suffered no clinical neurotoxicity from the human ortholog. These results strongly infer that toxicity of intrathecal IL-10 in large animal models was previously overlooked because of a species mismatch between transgene and host. The present study further suggests that swine were protected from interleukin-10 by a humoral immune response against the xenogeneic cytokine. Future safety studies of IL-10 or related therapeutics may require syngeneic large animal models.


Assuntos
Dependovirus/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Interleucina-10/genética , Transgenes , Animais , Anticorpos Antivirais/imunologia , Capsídeo/imunologia , Capsídeo/metabolismo , Dependovirus/imunologia , Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/efeitos adversos , Humanos , Injeções Espinhais , Interleucina-10/imunologia , Masculino , Modelos Animais , Suínos , Distribuição Tecidual , Transdução Genética
18.
Pain Med ; 19(3): 569-579, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29304236

RESUMO

Objective: The aim of this paper is to review the available literature investigating the effect of epidural steroid injections (ESIs) on bone mineral density (BMD) and vertebral fracture risk. Study design: Systematic review of current literature. Methods: The sources of the data were PubMed, Embase, Cochrane, and Scopus. Papers included in the review were original research articles in peer-reviewed journals. Results: A total of 7,233 patients (eight studies) with a mean age ranging between 49 and 74 years and an average follow-up between six and 60 months were studied. Steroids that were used included triamcinolone, dexamethasone, and methylprednisolone (MP), with a mean number of injections ranging from one to 14.7 and an average cumulative dose in MP equivalents between 80 and 8,130 mg. Epidural steroids were associated with significantly decreased BMD in four out of six included studies, and with increased risk of vertebral fracture in one out of two included studies. Significant reductions in BMD were associated with a cumulative MP dose of 200 mg over a one-year period and 400 mg over three years, but not in doses of less than 200 mg of MP equivalents for postmenopausal women and at least 3 g for healthy men. The risk of osteopenia and osteoporosis was lower in patients who were receiving anti-osteoporotic medication during the treatment course. Conclusions: ESIs should be recommended with caution, especially in patients at risk for osteoporotic fractures, such as women of postmenopausal age. Anti-osteoporotic medication might be considered prior to ESI.


Assuntos
Anti-Inflamatórios/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Dexametasona/administração & dosagem , Metilprednisolona/administração & dosagem , Fraturas da Coluna Vertebral/induzido quimicamente , Triancinolona/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Humanos , Injeções Epidurais , Masculino , Metilprednisolona/efeitos adversos , Fraturas da Coluna Vertebral/epidemiologia , Triancinolona/administração & dosagem
19.
Mol Ther ; 25(11): 2526-2532, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28822691

RESUMO

Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia. Necropsy demonstrated lymphocytic meningitis without evidence of infection in the presence of normal laboratory findings for body fluids and normal histopathology of peripheral organs. Results were replicated in a second animal cohort by a team of independent experimenters. An extensive infectious disease and neuropathology workup consisting of comprehensive testing of tissues and body fluids in a specialized research veterinary pathology environment did not identify a pathogen. These observations raise the concern that i.t. IL-10 therapy may not be benign, that previously used xenogeneic models testing the human homolog of IL-10 may not have been sensitive enough to detect toxicity, and that additional preclinical studies may be needed before clinical testing of IL-10 can be considered.


Assuntos
Ataxia/imunologia , Dependovirus/imunologia , Vetores Genéticos/administração & dosagem , Meningite Asséptica/imunologia , Convulsões/imunologia , Animais , Ataxia/induzido quimicamente , Ataxia/mortalidade , Ataxia/patologia , Dependovirus/genética , Avaliação Pré-Clínica de Medicamentos , Drogas em Investigação , Feminino , Terapia Genética/métodos , Vetores Genéticos/química , Vetores Genéticos/imunologia , Injeções Espinhais , Interleucina-10/genética , Interleucina-10/imunologia , Masculino , Meningite Asséptica/induzido quimicamente , Meningite Asséptica/mortalidade , Meningite Asséptica/patologia , Convulsões/induzido quimicamente , Convulsões/mortalidade , Convulsões/patologia , Análise de Sobrevida , Suínos
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