The Left Atrial Appendage, once thought to be "a relatively insignificant portion of cardiac anatomy," has currently been realized to possess "important pathological associations [1a]" particularly in its role in promoting serious, frequent thromboembolic events common in individuals suffering from Atrial Fibrillation. Prior approaches to mitigating these events have either required invasive procedures, proved less than fully effective, or presented with problematic sequelae of their own. This work will present a new procedure that addresses both the prevention of the thromboembolic events and the correction of the shortcomings of the major prior methods utilized. A compliant hydrogel that can conform to the geometry of the appendage is proposed as a more effective method of occluding the chamber. This material would be transported to the LAA in liquid form via a multi-lumen catheter, and then solidify within the chamber to form a solid plug. Previous research has identified a candidate hydrogel, comprised of PEG-tetra-thiol and Dextran vinyl sulfone as a candidate hydrogel for this application. Experimental work has investigated fluid properties of the material, as well as degradation and swelling properties of the material. Results from this experimentation were used for fluid transport analysis, and for evaluation of anchoring force of the hydrogel within the chamber. Finally, subfunctions of the occlusion procedure were modeled and tested. During the actual procedure, a catheter balloon will isolate the appendage from the rest of the heart. A model was developed to study interactions between the appendage and this balloon. Additionally, due to fast solidification time, hydrogel components in the surgical procedure will be mixed in a mixing chamber at the tip of the catheter. Potential mixing chamber designs were modeled, and a ternary diffusion model was developed to better understand hydrogel mixing. Prototypes for both these subfunctions were built and tested as well. Additional analysis looked at the overall occlusion procedure, and how various subfunctions interacted with each other. / text

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Background: Lung transplant is the fastest growing solid organ transplant procedure and venous thromboembolism has been described to occur in 8-29% of cases. This is much higher than any other solid organ and the exact incidence has yet to be determined. Risk factors for the development of venous thromboembolic disease (VTE) specific to lung transplant are not fully understood. Purpose: The purpose of this research was to describe the incidence and risk factors for VTE disease during the first year following lung transplant at a busy transplant center in the Southwest United States. Methods: A descriptive retrospective study design was used. Virchow's triad was used as a theoretical model to identify selected variables common to lung transplant in an effort to understand possible risk factors for the development of VTE in this patient population. Consecutive lung transplant cases between June 1, 2013 and May 31, 2014 at St. Joseph's Medical Center in Phoenix, Arizona were retrospectively reviewed and followed for exactly one year following the lung transplant date. Demographic variables, Virchow's triad variables, and variables previously identified in the literature as being risk factors for VTE were collected and analyzed using descriptive, frequency, t-test, chi-square, and logistic regression. Results: The incidence of VTE in this patient population was 25.8% and is consistent with findings from previous studies. Using the constructs of Virchow's triad did not yield any statistically significant predictors for VTE in this patient population. However, lung allocation score (LAS) (OR 1.109, CI 1.038-1.185), body mass index (BMI) (OR 1.362, CI 1.034-1.794), and time on the waitlist (OR 1.094, CI 1.023-1.171) did reach statistical significance as possible predictors for VTE following lung transplant in this patient sample. Conclusions: VTE is a common complication of lung transplant that has a high incidence during the first year following lung transplant. This study did identify LAS, BMI, and time on the waitlist as being possible risk factors for the development of VTE following lung transplant. LAS may be a useful surrogate to determine the risk for VTE in this population.

A disponibilidade de hemoderivados é um parâmetro importante para medir a qualidade da saúde em um país. Dentre os produtos hemoderivados, imunoglobulinas tem alto valor agregado. O Instituto Butantan tem por objetivo o estabelecimento de uma planta industrial para fracionamento de plasma, com um processo produtivo baseado principalmente em cromatografias. Eventos tromboembólicos a partir de infusões de imunoglobulinas por via intravenosa (IgIV) foram relacionados com presença de Fator XI de coagulação (FXI) como contaminantes nas preparações de IgIVs. Com objetivo de detectar o FXI nas frações, o processo cromatográfico foi testado em escala piloto, bancada, e em cromatografia direta e o FXI foi dosado nas frações iniciais e no produto final IgIV. Foram estabelecidos os métodos de dosagem de atividade de FXI por tempo de coagulação e ensaio cromogênico. Concluímos que o FXI acompanha a IgG nas etapas iniciais dos processos cromatográficos e verificamos que ocorre a presença de FXI nos produtos finais. Este trabalho contribui para o desenvolvimento do conjunto de testes de controle de qualidade de biofármacos derivados de plasma humano. / The availability of hemoderivatives is an important parameter to measure a countrys health quality. Among hemoderivatives products, immunoglobulin have high value.. Instituto Butantan, aims the establishment of an industrial plant for plasma fractionation with a process drawn, based mainly in chromatographies. Thromboembolic events from infusions of intravenous immunoglobulins (IVIg) have been related with the presence of coagulation Factor XI (FXI) as contaminant in the IVIG preparations. With an objective of tracking FXI in the chromatographic fractions, the process was tested in pilot and bench scales and in direct chromatography and the FXI was measured in the initial fractions and in the final product IVIg. The methods of measurement of FXI activity thru coagulation time and chromogenic assay were established. We have concluded that FXI accompanies IgG in the early stages of the chromatographic processes and verified that the presence occurs in the final products, This work contributes to the development of the set of quality control tests of biopharmaceuticals derivatives from human plasma.

<p>The laparoscopic way of performing general surgical procedures was introduced all over the Western world in a few years around 1990. No previous scientific studies of the safety of this new way of performing general surgery had been undertaken.</p><p>In an animal study, it was shown that carbon dioxide pneumoperitoneum (CO₂PP) causes an increase in inferior caval vein (ICV) pressure, although there were no effects on the ICV blood flow. There were gradual increases in systemic, pulmonary and ICV vascular resistance, which remained after exsufflation. These effects on vascular resistance could not be reproduced in a second animal study, presumably due to a different form of anesthesia. In this study, there was only indirect evidence of CO₂ PP decreasing urine output. No increase in vasopressin, which is commonly seen during CO₂ PP, was found, indicating that vasopressin may play a role in the decreased urine output during CO₂ PP but that there must be other contributing factors as well. Only brief effects on the renal arterial blood flow were seen.Renal venous pressure increased to that of the ICV.</p><p>A literature review indicated that thromboembolic complications do occur after laparoscopic cholecystectomy (LC). The relative frequencies indicated an underreporting of deep vein thrombosis (DVT) in relation to pulmonary embolism (PE).</p><p>In a clinical study, activation of the coagulation after LC was demonstrated. There were differences between the groups receiving dextran and low molecular weight heparin as prophylaxis. A further clinical study showed the incidence of DVT, as demonstrated by phlebography, to be 2.0 % (95 % confidence interval 0-6.0 %) 7-11 days after LC, even though thromboembolism prophylaxis was given in shorter courses than those scientifically proven to be effective against DVT. D-dimer values increased at the first postoperative day and even further at the time of phlebography, suggesting that the effects of LC on coagulation and/or fibrinolysis may be of longer duration than previously known.</p>

The laparoscopic way of performing general surgical procedures was introduced all over the Western world in a few years around 1990. No previous scientific studies of the safety of this new way of performing general surgery had been undertaken. In an animal study, it was shown that carbon dioxide pneumoperitoneum (CO2PP) causes an increase in inferior caval vein (ICV) pressure, although there were no effects on the ICV blood flow. There were gradual increases in systemic, pulmonary and ICV vascular resistance, which remained after exsufflation. These effects on vascular resistance could not be reproduced in a second animal study, presumably due to a different form of anesthesia. In this study, there was only indirect evidence of CO2 PP decreasing urine output. No increase in vasopressin, which is commonly seen during CO2 PP, was found, indicating that vasopressin may play a role in the decreased urine output during CO2 PP but that there must be other contributing factors as well. Only brief effects on the renal arterial blood flow were seen.Renal venous pressure increased to that of the ICV. A literature review indicated that thromboembolic complications do occur after laparoscopic cholecystectomy (LC). The relative frequencies indicated an underreporting of deep vein thrombosis (DVT) in relation to pulmonary embolism (PE). In a clinical study, activation of the coagulation after LC was demonstrated. There were differences between the groups receiving dextran and low molecular weight heparin as prophylaxis. A further clinical study showed the incidence of DVT, as demonstrated by phlebography, to be 2.0 % (95 % confidence interval 0-6.0 %) 7-11 days after LC, even though thromboembolism prophylaxis was given in shorter courses than those scientifically proven to be effective against DVT. D-dimer values increased at the first postoperative day and even further at the time of phlebography, suggesting that the effects of LC on coagulation and/or fibrinolysis may be of longer duration than previously known.

A disponibilidade de hemoderivados é um parâmetro importante para medir a qualidade da saúde em um país. Dentre os produtos hemoderivados, imunoglobulinas tem alto valor agregado. O Instituto Butantan tem por objetivo o estabelecimento de uma planta industrial para fracionamento de plasma, com um processo produtivo baseado principalmente em cromatografias. Eventos tromboembólicos a partir de infusões de imunoglobulinas por via intravenosa (IgIV) foram relacionados com presença de Fator XI de coagulação (FXI) como contaminantes nas preparações de IgIVs. Com objetivo de detectar o FXI nas frações, o processo cromatográfico foi testado em escala piloto, bancada, e em cromatografia direta e o FXI foi dosado nas frações iniciais e no produto final IgIV. Foram estabelecidos os métodos de dosagem de atividade de FXI por tempo de coagulação e ensaio cromogênico. Concluímos que o FXI acompanha a IgG nas etapas iniciais dos processos cromatográficos e verificamos que ocorre a presença de FXI nos produtos finais. Este trabalho contribui para o desenvolvimento do conjunto de testes de controle de qualidade de biofármacos derivados de plasma humano. / The availability of hemoderivatives is an important parameter to measure a countrys health quality. Among hemoderivatives products, immunoglobulin have high value.. Instituto Butantan, aims the establishment of an industrial plant for plasma fractionation with a process drawn, based mainly in chromatographies. Thromboembolic events from infusions of intravenous immunoglobulins (IVIg) have been related with the presence of coagulation Factor XI (FXI) as contaminant in the IVIG preparations. With an objective of tracking FXI in the chromatographic fractions, the process was tested in pilot and bench scales and in direct chromatography and the FXI was measured in the initial fractions and in the final product IVIg. The methods of measurement of FXI activity thru coagulation time and chromogenic assay were established. We have concluded that FXI accompanies IgG in the early stages of the chromatographic processes and verified that the presence occurs in the final products, This work contributes to the development of the set of quality control tests of biopharmaceuticals derivatives from human plasma.

Relation between the reperfusion of pulmonary arteries after acute pulmonary embolism to the development of chronic thromboembolic pulmonary hypertension Incomplete resolution of thromboemboli following acute pulmonary embolism (PE) is a key factor in development of chronic thromboembolic pulmonary hypertension (CTEPH). In our study, we evaluated the incidence, risk factors and clinical impact of incomplete reperfusion after acute PE. Study population and methods: 85 patients after the first acute PE were assessed clinically and by pulmonary scintigraphy and echocardiography at month 6, 12 and 24 after an acute PE. Results: Incomplete reperfusion was detected in 23.5 % of patients after 6 months, in 24.9 % of patients after 12 months and in 18.6 % of patients after 24 months. At month 6, patients with incomplete reperfusion were more obese when compared with patients with normal reperfusion BMI 30.8 vs 28.3 kg/m2 ; p=0.012) and their initial hemoglobin levels were higher (143.0 vs 136.0 g/l; p=0.012). Similar results were observed at month 12 - patients with residual perfusion defects were more obese (BMI 31.1 vs 28.5; p=0.016) with higher initial hemoglobin levels (144.0 vs 136.0; p=0.007). Patients with incomplete reperfusion at month 24 were significantly older (67.7 vs 55.0 years; p=0.02), their...

Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had 6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan–Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.

Comme dans tout cancer, l'association entre myélome multiple et maladie thrombo-embolique veineuse est bien établie. Son incidence au cours du myélome est en moyenne de 10 à 20%. Elle semble plus élevée en cas de myélome de novo et lors de l’utilisation de traitements immunomodulateurs comme le thalidomide. Pourtant, la part de surcroît du risque de thrombose dû à ce traitement n’est pas encore très bien définie. Tout d’abord, nous avons réalisé un bilan de ces pathologies afin de délimiter le champ d’étude grâce à une revue de la littérature. Nous avons ensuite évalué l’incidence de la maladie thrombo-embolique veineuse, identifié les facteurs de risque thrombotique et évalué le classement en groupe de risque des patients présentant un myélome et traités par immunomodulateur grâce à une étude observationnelle, multicentrique, prospective, de la prise en charge des myélomes par les hématologues en France. Par la suite, nous avons réalisé l’analyse médico-économique du seul essai randomisé réalisé à ce jour sur la thrombophylaxie chez les malades présentant un myélome multiple traités par thalidomide en première ligne. Cette étude montre un gain de qualité de vie associé à des économies majeures lors de la prévention de la thrombose par aspirine plutôt que par héparine. Enfin nous avons réalisé 2 études médicales utilisant la génération de thrombine, test biologique de recherche. La première a été effectuée afin d’essayer de prédire les patients qui vont présenter une thrombose. La deuxième a pour but de rechercher l’existence d’une résistance à l’héparine aux doses habituelles utilisées dans cette pathologie / The association between multiple myeloma and venous thromboembolic disease is well established. This incidence in myeloma is on average from 10 to 20%. It appears to be higher in newly diagnosed myeloma and immunomodulatory drugs such as thalidomide might significantly increase the risk. However, the risk of thrombosis due to these treatments is not yet well defined. First, we performed a review of these diseases in order to delimit the field of this study through a literature review. Then, we evaluated the incidence of venous thromboembolic disease in patients with myeloma and treated with immunomodulatory, identified the thrombotic risk factors and evaluated the thrombotic risk assessment based on the physicians choice, through an observational, multicenter, prospective French study. Moreover, we performed the medico-economic analysis of the only randomized trial conducted to date on the thrombophylaxis in patients with multiple myeloma treated with thalidomide in the first line of chemotherapy. This analysis showed a gain in quality of life associated with significant cost savings in the prevention of thrombosis by aspirin rather than heparin. Finally we performed two medical studies using thrombin generation test, a global assay that measures the overall tendency of a plasma sample to form thrombin. The first study was conducted to predict patients who will have thrombosis. The second is performed to know if a heparin resistance with the usual doses in this pathology, exists