INTRODUÇÃO: A cardiopatia chagásica (CC) é um importante problema de saúde pública na América do Sul e a patogênese desta doença ainda não é totalmente compreendida, mas a inflamação e a fibrose miocárdica participam de forma central no processo crônico e progressivo de dano miocárdico. Trabalho prévio de nosso grupo demonstrou a capacidade da Ressonância Magnética Cardiovascular (RMC) de identificar precisamente a fibrose miocárdica em pacientes com Doença de Chagas. A RMC demonstrou ser eficaz para avaliar edema miocárdico, como marcador de inflamação, e ser altamente sensível para a detecção de trombos intracavitários, especialmente no ventrículo esquerdo, e em outras patologias, como miocardites e infartos. A avaliação de edema miocárdio pela RMC em pacientes com CC não foi ainda avaliada na literatura. Nosso objetivo foi investigar a presença de edema e fibrose miocárdica nas três formas clínicas da CC, o que julgamos ser de potencial valor diagnóstico e prognóstico. MÉTODOS: Cinquenta e quatro pacientes com doença de chagas foram analisados: 16 pacientes com a forma indeterminada (FI), 17 pacientes com CC-SD e 21 pacientes com CC-CD. Todos os pacientes foram submetidos a exame de RMC em equipamento de 1,5 T, utilizando a sequência de realce tardio do miocárdio (RTM), a sequência de edema miocárdico (Spin-eco ponderado em T2) e a sequência de realce global precoce ponderado T1 pós-contraste, para identificar fibrose, edema e hiperemia miocárdicos, respectivamente. RESULTADOS: A fibrose miocárdica foi encontrada em 39 indivíduos, 72,2% de toda a amostra. A fibrose miocárdica foi detectada em 2 pacientes (12,5%) na forma indeterminada, com uma massa de fibrose média de 0,85 ± 2,47g. Os pacientes da forma CC-SD em sua quase totalidade - 16 pacientes (94,1%) - apresentaram fibrose, com uma massa média de 13,0 ± 10,8g. Todos os pacientes com a forma CC-CD apresentaram fibrose miocárdica (21 pacientes) e adicionalmente detinham a maior massa de fibrose média, 25 ± 11,9g. O edema miocárdico foi encontrado em 40 indivíduos, 74,0% de toda a amostra. A extensão do edema miocárdico foi analisada pelo número de segmentos comprometidos. Foram identificados 3 pacientes (18,8%) da forma indeterminada com critérios positivos para edema miocárdio, determinando uma média de 0,31 ± 0,87 segmentos. A forma CC-SD obteve a presença de edema em 16 indivíduos (94,1%) distribuídos em uma média de 3,24 ± 2,3 segmentos. Todos os pacientes da forma CC-CD apresentaram edema miocárdico pela RMC, em uma média 3,67 ± 1,82 segmentos (p < 0,001). Houve correlação significativa entre a quantidade de fibrose miocárdica e edema miocárdico com a gravidade das formas clínicas (p < 0,001), classe funcional (p < 0,001), fração de ejeção do VE (p < 0,001) e volume diastólico do VE(p < 0,001). CONCLUSÃO: Fibrose e inflamação miocárdica foram detectadas pela ressonância magnética cardíaca em pacientes portadores de cardiopatia chagásica em todas as fases crônicas da doença, inclusive naqueles pacientes sem cardiopatia ou com cardiopatia sem disfunção ventricular. A quantidade de fibrose e edema miocárdico apresenta correlação com a gravidade da forma clínica, classe funcional, fração de ejeção do VE e dilatação do VE / BACKGROUND AND PURPOSE: Chagas\' heart disease (CHD) is a major public health problem in South America, and the pathogenesis of this disease is not yet fully understood, but inflammation and myocardial fibrosis seem to play a central role in the process of chronic and progressive myocardial damage. Previous descriptions from our group demonstrated the ability of Cardiovascular Magnetic Resonance (CMR) accurately identify myocardial fibrosis in patients with CHD. CMR shown to be effective for assessing myocardial edema, a marker of inflammation, and is highly sensitive for the detection of thrombi, especially in the left ventricle in other pathologies such as myocarditis and myocardial infarct. The assessment of myocardial edema by CMR in patients with CHD has not been evaluated. We believe to be of potential diagnostic and prognostic value to investigate the presence of myocardial edema and fibrosis in patients in the three clinical forms of this disease. METHODS: Fifty-four patients with Chagas\' disease were analyzed: 16 patients with the indeterminate phase (IF), 17 patients with the cardiac form without left ventricular systolic dysfunction (CFWO), and 21 patients with the cardiac form with left ventricular systolic dysfunctional form (CFSD). All patients underwent 1.5-T cardiac magnetic resonance (CMR) using the myocardial delayed enhancement sequence (MDE), T2-weighted sequence and the T1 weighted global enhancement after contrast sequence, to identify fibrosis, edema and hyperemia, respectively. RESULTS: Myocardial fibrosis was found in 39 subjects, 72.2% of the entire sample. Myocardial fibrosis was detected in 2 patients (12.5%) with the indeterminate form, representing an average mass of fibrosis of 0.85 ± 2.47 g. Patients with the CFWO almost entirely, 16 patients (94.1%) showed fibrosis, representing an average mass of fibrosis of 13.0 ± 10.8 g. All patients with the CFSD had myocardial fibrosis (21 patients) additionally had greater average mass of fibrosis 11.9 ± 25g. The myocardial edema was found in 40 subjects, 74.0% of the entire sample. The extent of myocardial edema was determined by the number of segments affected. We identified three patients (18.8%) from the indeterminate form with myocardial edema, an average of 0.31 ± 0.87. The CFWO presented a high presence of edema in 16 individuals (94.1%) distributed in an average of 3.24 ± 2.3 segments. All patients with the CFSD presented myocardial edema, an average of 3.67 ± 1.82 segments. (p < 0.001). There was significant correlation between the amount of myocardial fibrosis and myocardial edema with the severity of the clinical forms ( p < 0.001 ), functional class ( p < 0.001 ), LV ejection fraction ( p < 0.001 ) and left ventricular diastolic volume ( p < 0.001). CONCLUSION: Myocardial fibrosis and inflammation were detected by cardiac magnetic resonance imaging in patients with Chagas\' disease in all stages of chronic disease, including those patients without heart disease or cardiomyopathy without ventricular dysfunction. The amount of fibrosis and myocardial edema correlates with the severity of the clinical, functional class, LV ejection fraction and LV dilation

INTRODUÇÃO: Durante o esvaziamento cervical, além do tecido linfático, algumas estruturas não-linfáticas do pescoço estão sob risco de lesões ou são ressecadas, dentre as quais se encontra a veia jugular interna. Esta é diretamente relacionada com a drenagem venosa e linfática da face e do pescoço e, sua ressecção, pode ocasionar congestão venosa, edema de face e laríngeo, distúrbios visuais e edema cerebral. Há várias técnicas para avaliar o edema, todavia, não há relatos de uma técnica objetiva que possa ser utilizada na região da cervicofacial. Esse estudo teve por objetivo mensurar o edema em pontos específicos localizados na face e no pescoço em indivíduos submetidos a esvaziamento cervical com ou sem ressecção da veia jugular interna. MÉTODOS: Esse estudo utiliza um método objetivo de mensuração do edema na face e no pescoço de indivíduos no pré e no pós-operatório de esvaziamento cervical unilateral ou bilateral com ou sem ressecção da veia jugular interna, por doença maligna na região da cabeça e pescoço e sem tratamento prévio no pescoço, através do medidor da constante dielétrica da pele e da gordura subcutânea em quatro momentos: pré-operatório, 3º, 10º e 30º dia de pós-operatório, em pacientes tratados no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital A. C. Camargo. RESULTADOS: Foram avaliados prospectivamente 51 pacientes, sendo a maioria do sexo masculino (68,6%) com idade média de 55,7 anos (mediana de 54 anos). Observou-se que a constante dielétrica do tecido não se apresentou estatisticamente diferente entre os pacientes com e sem ressecção da veia jugular interna, entretanto, nos pacientes submetidos a esvaziamento cervical unilateral houve edema significativo entre o pré e o pós-operatório tanto naqueles com preservação como naqueles com ressecção da veia, assim como nos bilaterais com preservação da mesma, afetando em ambos os grupos a qualidade de vida em geral e em relação à aparência. Verificou-se também que o edema parece ser inevitável após o procedimento, pois o mesmo foi evidenciado de forma significativa nos pacientes submetidos a esvaziamento cervical radical, radical modificado e seletivo. CONCLUSÕES: Não há diferença significativa em relação ao edema cervicofacial após o esvaziamento cervical entre os pacientes com e sem ressecção da veia jugular interna, entretanto, há diferença entre o pré e o pós-operatório em cada grupo independente da preservação ou não da veia, sendo os pontos mais afetados a região mandibular e do pescoço / INTRODUCTION: During neck dissection, besides the lymphatic tissue, some non-lymphatic structures of the neck are at injury risk or are resected, such as the internal jugular vein. This is directly related to venous and lymphatic drainage of face and neck, and, thus, resection may cause venous congestion, facial and laryngeal edema, visual disturbances and cerebral edema. There are several techniques to evaluate the edema; however, there are no reports of a particular technique that can be used in the facial region. This study aimed to quantify edema in specific points sited at the face and neck of patients who underwent neck dissection with or without resection of the internal jugular vein. METHODS: These study uses an objective method of facial and neck edema measurement of patients at pre and postoperative of unilateral or bilateral neck dissection with or without internal jugular vein resection, for malignancies at the head and neck level and with no previous neck treatment, through a device that assess the skin dielectric constant and subcutaneous fat in four stages: preoperative, 3rd, 10th and 30th postoperative days, in patients treated at the A. C. Camargo Hospital Head and Neck Department, Sao Paulo, Brazil. RESULTS: There were 51 patients prospectively evaluated; mostly males (68.6%) with mean age of 55.7 years (median of 54 years). It was verified that differences on tissue dielectric constant were not statistically different between patients with and without internal jugular vein resection; however, in patients undergone unilateral neck dissection there was significant edema between pre and postoperative both in those with preserved vein as in those with resection, as well as in bilateral with vein preservation, affecting the general quality of life and the one related to appearance in both groups. It was also found that edema seems to be unavoidable after the procedure, as it was evidenced significantly in patients undergoing radical neck dissection, modified radical and selective. CONCLUSION: No significant difference was observed in face and neck edema after neck dissection in patients with or without internal jugular vein resection, however, there is difference between pre and postoperative in each group regardless of the preservation or not of the vein, where the most affected points are mandible and neck

Un endothélium vasculaire rétinien quiescent est essentiel dans l’approvisionnement et le maintien de l’homéostasie tissulaire afin d’assurer la fonction visuelle. L’hyperglycémie chronique dans le diabète peut mener à des complications reliées à plusieurs changements structuraux et fonctionnels de l’endothélium. Ces changements se manifestent souvent par des vaisseaux instables et hyperperméables, résultant en un tissu rétinien inadéquatement perfusé. Ces altérations sont rencontrées dans la pathophysiologie de l’œdème maculaire diabétique (OMD) qui affecte plus du quart des diabétiques. L’inhibition du facteur de perméabilité vasculaire VEGF-A a révolutionné le traitement de l’OMD, mais est aussi associée à des effets secondaires non négligeables reliés à leur non-spécificité et à une compréhension incomplète des mécanismes régulant la perméabilité vasculaire. Un ciblage spécifique de l’endothélium permettant la récupération de la quiescence et la stabilité physiologique réduisant l’hyperperméabilité pourrait fournir un nouvel outil thérapeutique. La BMP9 (Bone morphogenetic protein 9), qui est mise en circulation par le foie, est connue comme facteur de quiescence et de stabilité vasculaire ainsi que pour son effet sur l’homéostasie du glucose. Ces aspects étant peu documentés dans un contexte diabétique, nous avons évalué les capacités de la BMP9 sur la stabilisation de l’endothélium rétinien et ses effets paracrines/autocrines sur la gluconéogenèse hépatique. Nous avons démontré que la signalisation canonique de la BMP9/Smad1,5,9 via son récepteur spécifique à l’endothélium Alk1, était déficiente dans un modèle murin de diabète, ce qui exacerbe l’hyperperméabilité endothéliale rétinienne. À l’inverse, la surexpression de la BMP9 par un modèle murin de livraison adénovirale récupère la perméabilité physiologique, associée principalement à un renforcement des jonctions interendothéliales en limitant l’action du VEGF. De plus, nous avons trouvé que la BMP9 améliore le contrôle glycémique chez les souris diabétiques par l’inhibition de la gluconéogenèse hépatique, via la voie non-canonique Alk3/FOXO1. Fondamentalement, ce travail met en évidence les mécanismes régissant la perméabilité endothéliale dans un contexte diabétique, fournissant une alternative thérapeutique contre l’OMD. La régulation de la perméabilité rétinienne par la BMP9 s’effectue à plusieurs niveaux, indirectement par le contrôle glycémique, et directement par la solidification jonctionnelle de la barrière endothéliale rétinienne, réhabilitant ainsi la quiescence et la stabilité de l'endothélium physiologique. / A quiescent retinal vascular endothelium is essential for the supply and maintenance of tissue homeostasis to ensure proper visual function. Chronic hyperglycemia in diabetes can lead to multiple complications related to several structural and functional changes in the endothelium, characterized by unstable and hyperpermeable vessels resulting in an inadequately perfused retinal tissue. These alterations are encountered in the pathophysiology of diabetic macular edema (DME), which affects more than a quarter of diabetics. Inhibition of the vascular permeability factor VEGF-A has revolutionized the treatments of DME but is associated with non-negligible side effects related to their non-specific action combined with an incomplete understanding of the mechanisms regulating vascular permeability. Specific endothelial targeting aiming to recover quiescence and reducing hyperpermeability could provide new therapeutic tools for the treatment or prevention of DME. BMP9 (Bone morphogenetic protein 9), which is produced by the liver, is known as a vascular quiescence and stability factor as well as for its effects on glucose homeostasis. Since these aspects are poorly documented in a diabetic context, we investigated BMP9’s capabilities on endothelium stabilization and its paracrine/autocrine effects on hepatic gluconeogenesis. In our studies, we found that the canonical BMP9/Smad1,5,9 signaling, via its physiological Alk1 endothelium-specific receptor, was deficient in a murine model of diabetes, which exacerbates retinal endothelial hyperpermeability. In contrast, adenoviral overexpression of BMP9 recovers physiological permeability, which was primarily associated with the enhancement of interendothelial junctions by limiting the action of VEGF. In addition, we found that BMP9 improves glycemic control in diabetic mice by inhibition of hepatic gluconeogenesis via the non-canonical ALK3/FOXO1 pathway. Fundamentally, this work highlights new insights of the mechanisms governing endothelial permeability in a diabetic context, providing a therapeutic alternative against DME. Regulation of retinal permeability by BMP9 occurs on several levels, indirectly, through glycemic control, and directly through the junctional solidification of the hyperglycemic retinal endothelial barrier, thus rehabilitating the quiescence and stability of the physiological endothelium.

Master of Science / Department of Horticulture, Forestry, and Recreation Resources / Kimberly A. Williams / Ivy geranium (Pelargonium peltatum L’Herr ex. Ait.) and tomato (Solanum lycopersicum L.) are two economically important greenhouse crops known to be affected by non-pathogenic lesions on leaf tissues. These physiological disorders are often termed edema (oedema) or intumescences, but several other names have been used including enations, non-pathogenic galls or tumors, and neoplasms. These lesions, characterized by small protrusions on leaf tissues that become necrotic over time, are considered to be the result of environmental factors. Our research focused on determining what environmental factors affect these disorders on ivy geranium and tomato. The physiological disorder of ivy geranium is thought to be the result of water uptake exceeding transpiration, resulting in a build-up of water and solutes in leaf tissue that results in the blister-like protrusions in the epidermal layer. Current convention suggests that susceptible plants be grown in an environment that promotes transpiration with low humidity and infrequent watering. Over four experiments, we evaluated the effects of four root medium water contents, five rates of supplemental calcium application and two vapor pressure deficit (VPD) environments on three cultivars of ivy geranium. Our results indicate that high root medium water contents do not increase the incidence of edema on ivy geranium, but increase overall plant growth. Supplemental calcium had no affect on edema or growth, while our VPD results were inconclusive. These results suggest that current convention regarding cultural practices that abate the disorder be revisited. In tomato var. hirsutum ‘Maxifort’, the physiological disorder is characterized by individual epidermal cells swelling, which is unlike the disorder in ivy geranium where solutes build up across a group of epidermal cells. The environmental factors we focused on were two root medium water contents and supplemental UVB light. Our results suggest that root medium water content may play a role in development of tomato intumescences based on visual observation, and UVB light supplementation helps prevent the lesions from forming.

BACKGROUND: The abnormal signal intensity in cardiac T₂-weighted images is associated with various pathologies including myocardial edema. However, the assessment of pathologies based on signal intensity is affected by the acquisition parameters and the sensitivities of the receiver coils. T₂ mapping has been proposed to overcome limitations of T₂-weighted imaging, but most methods are limited in spatial and/or temporal resolution. Here we present and evaluate a double inversion recovery radial fast spin-echo (DIR-RADFSE) technique that yields data with high spatiotemporal resolution for cardiac T₂ mapping. METHODS: DIR-RADFSE data were collected at 1.5 T on phantoms and subjects with echo train length (ETL) = 16, receiver bandwidth (BW) = +/-32 kHz, TR = 1RR, matrix size = 256 x 256. Since only 16 views per echo time (TE) are collected, two algorithms designed to reconstruct highly undersampled radial data were used to generate images for 16 time points: the Echo-Sharing (ES) and the CUrve Reconstruction via pca-based Linearization with Indirect Echo compensation (CURLIE) algorithm. T₂ maps were generated via least-squares fitting or the Slice-resolved Extended Phase Graph (SEPG) model fitting. The CURLIE-SEPG algorithm accounts for the effect of indirect echoes. The algorithms were compared based on reproducibility, using Bland-Altman analysis on data from 7 healthy volunteers, and T₂ accuracy (against a single-echo spin-echo technique) using phantoms. RESULTS: Both reconstruction algorithms generated in vivo images with high spatiotemporal resolution and showed good reproducibility. Mean T₂ difference between repeated measures and the coefficient of repeatability were 0.58 ms and 2.97 for ES and 0.09 ms and 4.85 for CURLIE-SEPG. In vivo T₂ estimates from ES were higher than those from CURLIE-SEPG. In phantoms, CURLIE-SEPG yielded more accurate T₂s compared to reference values (error was 7.5-13.9% for ES and 0.6-2.1% for CURLIE-SEPG), consistent with the fact that CURLIE-SEPG compensates for the effects of indirect echoes. The potential of T₂ mapping with CURLIE-SEPG is demonstrated in two subjects with known heart disease. Elevated T₂ values were observed in areas of suspected pathology. CONCLUSIONS: DIR-RADFSE yielded TE images with high spatiotemporal resolution. Two algorithms for generating T₂ maps from highly undersampled data were evaluated in terms of accuracy and reproducibility. Results showed that CURLIE-SEPG yields T₂ estimates that are reproducible and more accurate than ES.

Following trauma, such as an impact injury or stroke, brain tissue can swell. Swelling is the result of water accumulation in the tissue that is driven by pathological changes, such as increased permeability of the capillary walls and osmotic pressure changes within the tissue. Swelling causes increased intracranial pressure and mechanical deformation of the brain tissue, exacerbating the original injury. Furthermore, prolonged local swelling can lead to the spread of damage to the (initially undamaged) surrounding tissue, since compression and increased intracranial pressure may restrict blood flow in this tissue. In this thesis, we develop mathematical models to examine the consequences of pathophysiological damage mechanisms on the swelling, and associated stress and strain, experienced by brain tissue. Mixture theory is used to represent brain tissue as a mixture of elastic solid, fluid and solutes. This modelling approach allows elastic deformations to be coupled with hydrodynamic pressure and osmotic gradients; the consequences of different mechanisms of damage may then be quantified. We consider three particular problems motivated by experimental observations of swelling brain tissue. Firstly, we investigate the swelling of isolated, damaged, brain tissue slices; we show that mechanisms leading to an osmotic pressure difference between the tissue slice and its surroundings can explain experimental observations for swollen tissue slices. Secondly, we use our modelling approach to demonstrate that local changes in capillary permeability can cause significant stresses and strains in the surrounding tissue. Thirdly, we investigate the conditions under which a locally swollen, damaged, region can cause compression of the vasculature within the surrounding tissue, and potentially result in damage propagation. To do this, we propose a coupled model for the oxygen concentration within, and mechanical deformation of, brain tissue. We use our model to assess the impact of treatment strategies on damage propagation through the tissue, and show that performing a craniectomy reduces the extent of propagation.

Targeted drug delivery to the brain is difficult to achieve using conventional techniques, largely due to the blood-brain barrier’s (BBB) impediment to drug diffusion into the brain parenchyma. In response, development of convection-enhanced delivery (CED) offers the ability to circumvent the BBB and target specific areas of the brain. Predictability of infusate movement in pathological brain states during CED will maximize the effectiveness of this treatment, and therefore modeling of infusate movement must be characterized. Previous work from our lab effectively modeled CED in rats using the middle carotid artery occlusion model of cytotoxic edema. However, previous models examined for vasogenic edema study did not show pure vasogenic edema. The purpose of this study was to develop a model of pure vasogenic edema in the rat brain. In this study, we show that stereotactic 9 µL infusion of 1.0 mM DCA over 45 minutes into the rat corpus callosum reproducibly creates pure vasogenic edema, as observed in the peritumoral white matter surrounding gliomas.

Abstract Background The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and mortality. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Pulmonary edema is a hallmark of VILI and the severity of edema increases with age. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress (ARDS) patients, but has not been investigated in VILI. We hypothesized that age-associated increases in pulmonary edema promote age-related increases in ventilator-associated mortality. Endoplasmic reticulum (ER) stress can disrupt cellular functions and plays a key role in many disease states. The severity of ER stress also increases with age. We hypothesized that age-associated increases in ER stress also increase in the severity of VILI. Finally, serum Vitamin C (VitC) levels also decrease with age. VitC treatments have been shown to decrease mortality rates in murine models of ARDS by and attenuate pulmonary edema. We hypothesize that VitC treatments will attenuate ventilator induced pulmonary edema in our aged murine subjects. Methods Mechanical Ventilation: Young and old mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for with either liberal or conservative fluid support. One group received VitC treatment prior to ventilation. Cell Stretch: Alveolar epithelial cells (ATIIs) from young and old mice were harvested, cultured, and mechanically stretched. Treatment groups received ER stress inhibitor 4-PBA. Results Both advanced age and HVT ventilation significantly increased inflammation, injury, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema decreased mortality rates. VitC treatments significantly decreased pulmonary edema and improved pulmonary mechanics. Mechanical stretch promoted ER Stress and upregulated proinflammatory gene expression and secretion in aged ATIIs. ER stress inhibition attenuated all of these effects. Conclusion Conservative fluid management alone attenuated age-associated increases in ventilator-associated mortality. VitC treatments decreased pulmonary edema and partially restore pulmonary mechanics in old mice ventilated with HVT. ER stress inhibition decreased stretch induced proinflammatory gene expression and protein secretion in aged mechanically stretched ATII cells.

OBJETIVO: Determinar a efetividade de manobras padronizadas de drenagem linfática manual (DLM) na redução do edema facial, na distância interincisal máxima ativa e no quadro álgico de pacientes submetidos à cirurgia de Enxerto Ósseo Alveolar (EOA). METODOLOGIA: Esta pesquisa analisou 51 indivíduos com fissura labiopalatina reparada, entre 10 e 15 anos de idade, submetidos ao EOA no Hospital de Reabilitação de Anomalias Craniofaciais-USP, divididos em 2 grupos, grupo tratamento (n=29, 12 homens e 17 mulheres) e grupo rotina (n= 22, 15 homens e 7 mulheres). No grupo tratamento foram aplicadas manobras de DLM padronizadas diferentemente daqueles do grupo rotina. Foram realizadas nos dois grupos avaliações do edema facial por meio das medidas da linha 1 (distância da base da asa nasal ao tragus) e linha 2 (distância da base da asa nasal à implantação inferior do pavilhão auricular), na hemiface operada nos períodos pré-operatório (Pré), segundo (2ºPO) e quarto pós-operatório (4ºPO). Também foram realizadas as medidas da distância interincisal máxima ativa nos mesmos períodos. A Escala Analógica da Dor (EAD) foi aplicada no 1º, 2º, 3º e 4º períodos pós-operatórios. Adicionalmente, no grupo tratamento, após a terapia de DLM, foram realizadas perguntas sobre dor, relaxamento e sono. RESULTADOS: Houve redução do edema facial no grupo tratamento do 2ºPO para o 4ºPO o que não ocorreu no grupo rotina. As medidas da distância interincisal apresentaram aumento entre o 2ºPO e 4ºPO nos dois grupos estudados. Na avaliação da EAD, o grupo tratamento mostrou ausência de dor no 3ºPO enquanto o grupo rotina somente no 4ºPO. No grupo tratamento, a totalidade dos indivíduos relataram que a dor diminuiu, e que se sentiram mais relaxados após a DLM, nos 3 períodos avaliados. Relataram também em muitos casos que a DLM teve efeito facilitador na indução ao sono durante a DLM. CONCLUSÕES: As manobras padronizadas de DLM aplicadas da maneira proposta produziram redução significante do edema facial, aumento da distância interincisal máxima ativa, redução do quadro álgico no grupo tratamento comparativamente ao grupo rotina. Esses dados reforçam a hipótese de que a DLM proposta foi efetiva contribuindo de maneira importante na recuperação do paciente submetido à cirurgia de EOA. / OBJECTIVE: To determine the effectiveness of standardized manual lymphatic drainage (MLD) maneuvers in reducing facial swelling, maximum interincisal active distance and pain of patients undergoing surgery for Alveolar Bone Grafting (ABG). METHODS: This study examined 51 individuals with repaired cleft lip and palate, aged 10 to 15 years old, who underwent ABG at the Hospital for Rehabilitation of Craniofacial Anomalies- USP, divided into two groups: treatment group (n = 29, 12 men and 17 women) and routine group (n = 22, 15 men and 7 women). In the treatment group MLD standardized maneuvers were performed differently from those of the group routine. In both groups evaluation of facial swelling was performed by measuring the distance from the ala nasi to the tragus (line 1) and the distance from the ala nasi to the inferior portion of the ear auricle (line 2), in the operated side, preoperatively, and at the second and the fourth postoperative (PO) day. The maximum active interincisal distance was measured during the same periods. The Pain Analog Scale (PAS) was applied at the first, second, third and fourth days after ABG. Additionally, patients from the treatment group, were asked about pain, relaxation and sleep after MLD therapy. RESULTS: There was a reduction of facial edema in the treatment group from the 2nd to 4th PO what was not observed the routine group. Interincisal distance increased between the 2nd and 4th PO in both groups. PAS evaluation has shown that patients from the treatment group present no pain already at 3rd PO. In the routine group this occurred only at 4th PO. All the subjects from treatment group reported decrease of pain, and patients reported felt more relaxed after the MLD, at the three postoperative evaluated. Many patients reported that MLD had a facilitative effect on inducing sleep during MLD. CONCLUSIONS: The standardized MLD maneuvers applied in the proposed manner produced significant reduction of facial swelling, increase of the maximum active interincisal distance, reduction of the pain in the treatment group as compared to the routine group.These Abstract data reinforce the hypothesis that the proposed MLD is a effective procedure for the recovery of the patients undergoing ABG surgery.

Introdução: Descontinuação prematura ou tardia da ventilação mecânica invasiva (VM) associa-se a maior morbimortalidade. Redução da pressão intratorácica durante o teste de respiração espontânea (TRE) pode precipitar disfunção cardíaca através da elevação abrupta do retorno venoso e da pós-carga do ventrículo esquerdo. Da mesma maneira, alterações na demanda respiratória e cardíaca que ocorrem ao longo do TRE também podem manifestar-se à ultrassonografia pulmonar. O padrão B é um artefato sonográfico que se correlacionada com edema intersticial. Um ensaio clínico randomizando concluiu que a ultrassonografia pulmonar foi capaz de prever insuficiência ventilatória pós extubação através de variações na aeração pulmonar observadas durante o procedimento de desmame; contudo, a ferramenta não pôde rastrear pacientes antes da submissão ao TRE. O impacto do balanço hídrico (BH) e de sinais radiológicos de congestão pulmonar antes do TRE sobre os desfechos no desmame também precisam ser determinados. Métodos: Cinquenta e sete indivíduos elegíveis para o desmame ventilatório foram recrutados. Traqueostomizados foram excluídos. Realizou-se avaliação ultrassonográfica de seis zonas pulmonares imediatamente antes e ao final do TRE. Predominância B foi definida como qualquer perfil com padrão B presente bilateralmente em região torácica anterior. Os pacientes foram seguidos por até 48 horas depois da extubação. Após esse estudo piloto, foi conduzido um estudo observacional, prospectivo, multicêntrico em duas unidades de terapia intensiva (UTIs) clínico-cirúrgicas ao longo de dois anos. Os mesmos critérios de inclusão e de exclusão foram aplicados; contudo, a ultrassonografia foi realizada apenas antes do TRE. O desfecho primário foi falha no TRE, definido como incapacidade de tolerar o teste T durante 30 a 120 minutos e, nesse caso, o paciente não era extubado. Dados demográficos e fisiológicos, BH das 48 horas antecedendo o TRE (entrada de fluidos menos débitos durante 48 horas) e desfechos foram coletados. Em uma análise post hoc de 170 procedimentos de desmame, um radiologista aplicou um escore radiológico na interpretação de radiografias digitais de tórax realizadas previamente ao TRE – o exame mais recente disponível foi avaliado em termos de congestão pulmonar. Resultados: No estudo piloto, 38 indivíduos foram extubados com sucesso, 11 falharam no TRE e 8 necessitaram de reintubação em até 48 horas após a extubação. No início do teste T, padrão B ou consolidação já estava presente em porções inferiores e posteriores dos pulmões em mais da metade dos casos, e tais regiões mantiveram-se não aeradas até o final do teste. Perda de aeração pulmonar durante o TRE foi observada apenas no grupo que falhou no mesmo (p= 0,07). Esses pacientes também demonstraram maior predominância B ao final do teste (p= 0,019). Antes do procedimento de desmame, todavia, não foi possível discernir indivíduos que falhariam no TRE, tampouco aqueles que necessitariam de reintubação dentro de 48 horas. Posteriormente, de 2011 a 2013, 250 procedimentos de desmame foram avaliados. Falha no TRE ocorreu em 51 (20,4%). Cento e oitenta e nove pacientes (75,6%) foram extubados na primeira tentativa. Indivíduos que falharam no TRE eram mais jovens (mediana de 66 versus 75 anos, p= 0,03) e apresentaram maior duração de VM e maior prevalência de doença pulmonar obstrutiva crônica (DPOC) (19,6 versus 9,5%, p= 0,04). Predominância B mostrou-se um preditor muito fraco para falha no TRE, exibindo sensibilidade de 47%, especificidade de 64%, valor preditivo positivo de 25% e valor preditivo negativo de 82%. Não houve diferença estatisticamente significativa no BH das 48 horas antecedendo o TRE entre os grupos (falha no TRE: 1201,65 ± 2801,68 ml versus sucesso no TRE: 1324,39 ± 2915,95 ml). Entretanto, em pacientes portadores de DPOC, ocorreu associação estatisticamente significativa entre BH positivo nas 48 horas antes do TRE e falha no TRE (odds ratio= 1,77 [1,24 – 2.53], p= 0,04). O escore radiológico, obtido em 170 testes T, foi similar entre os pacientes com falha e sucesso no TRE (mediana de 3 [2 – 4] versus 3 [2 – 4]), p= 0, 15). Conclusão: Maior perda de aeração pulmonar observada à ultrassonografia durante o TRE pode sugerir disfunção cardiovascular e aumento na água extravascular, ambos induzidos pelo processo de desmame. BH, sinais radiológicos de congestão pulmonar ou padrão B documentado através de um protocolo ultrassonográfico simplificado não devem contraindicar o TRE em pacientes estáveis hemodinamicamente e adequadamente oxigenados, haja vista o fato de tais variáveis não terem predito maior probabilidade de falha de desmame em pacientes críticos clínico-cirúrgicos. Ainda assim, evitar BH positivo em pacientes com DPOC parece otimizar os desfechos do desmame. / Introduction: Both delayed and premature liberation from mechanical ventilation (MV) are associated with increased morbi-mortality. Inspiratory fall in intra-thoracic pressure during spontaneous breathing trial (SBT) may precipitate cardiac dysfunction through abrupt increase in venous return and in left ventricular afterload. Changes in respiratory and cardiac load occurring throughout SBT might manifest with dynamic changes in lung ultrasound (LUS). B-pattern is an artifact that correlates with interstitial edema. A randomized controlled trial concluded that bedside LUS could predict post extubation distress due to changes in lung aeration throughout weaning procedure; however, it could not screen patients before submission to SBT. The impact of fluid balance (FB) as well as of radiological signs of pulmonary congestion prior to SBT on weaning outcomes must also be determined. Methods: Fifty-seven subjects eligible for ventilation liberation were enrolled. Patients with tracheostomy were excluded. LUS assessment of six thoracic zones was performed immediately before and at the end of SBT. B-predominance was defined as any profile with anterior bilateral B-pattern. Patients were followed up to 48 hours after extubation. After this pilot report, we conducted a 2-year prospective, multicenter, observational study in two adult medical surgical intensive care units (ICUs). Same inclusion and exclusion criteria were applied; however, LUS was performed only immediately before SBT. The primary outcome was SBT failure, defined as inability to tolerate a T-piece trial during 30 to 120 minutes, in which case patients were not extubated. Demographic, physiologic, FB in the preceding 48 hours of SBT (fluid input minus output over the 48-hour period), and outcomes data were collected. As a post hoc analysis in 170 weaning procedures performed in one of the ICUs, an attending radiologist applied a radiological score on interpretation of digital chest x-rays performed before SBT - the most recent available exam was analyzed regarding degree of lung fluid content. Results: In the pilot study, 38 subjects were successfully extubated, 11 failed the SBT and 8 needed reintubation within 48 hours of extubation. At the beginning of T-piece trial, B-pattern or consolidation were already found at lower and posterior lung regions in more than half of the individuals and remained nonaerated at the end of the trial. Loss of lung aeration during SBT was observed only in SBT-failure group (p= 0.07). These subjects also exhibited higher B-predominance at the end of trial (p= 0.019). Prior to weaning procedure, however, we were not capable to discriminate individuals who would fail SBT, nor who would need reintubation within 48 hours. Afterwards, from 2011 to 2013, 250 weaning procedures were evaluated. SBT failure occurred in 51 (20.4%). One hundred eighty-nine patients (75.6%) were extubated at first attempt. Individuals who failed SBT were younger (median 66 versus 75 years, p= 0.03), had higher duration of MV (median 7 versus 4 days, p< 0.0001) and higher prevalence of chronic obstructive pulmonary disease (COPD) (19.6 versus 9.5%, p= 0.04). B-predominance was a very weak predictor for SBT failure, showing 47% sensitivity, 64% specificity, 25% positive predictive value, and 82% negative predictive value. There were no statistically significant differences in 48 hour-FB prior to SBT between groups (SBT failure: 1201.65 ± 2801.68 mL versus SBT success: 1324.39 ± 2915.95 mL). However, in COPD subgroup, we found significant association between positive FB in the 48 hours prior to SBT and SBT failure (odds ratio = 1.77 [1.24 – 2.53], p= 0.04). Radiological score, obtained in 170 T-piece trials, was similar between SBT failure and success subjects (median 3 [2 - 4] vs 3 [2 - 4], p= 0.15). Conclusion: Higher loss of lung aeration observed by LUS during SBT might suggest cardiovascular dysfunction and increases in extravascular lung water, both induced by weaning. Neither FB, nor radiological findings of pulmonary congestion, nor B-pattern detected by a simplified LUS protocol should preclude hemodynamically stable, sufficiently oxygenated patients from performing an SBT, since such variables did not predict greater probability of weaning failure in medical-surgical critically ill population. Notwithstanding, avoiding positive FB in COPD patients might improve weaning outcomes.