Trombosis Venosa Retiniana y Trombosis Venosa Profunda; ¿hablamos de dos manifestaciones de una misma enfermedad? Estudio comparativo de 2 cohortes.

La oclusión venosa retiniana (OVR) es un trastorno vascular retiniano muy frecuente (la 2ª en frecuencia tras la retinopatía diabética), poco conocida y una importante causa de pérdida de visión. Su prevalencia varía de un 0,3-1,6% y aumenta con la edad, sobre todo a partir de los 65 años. Su etiopatogenia está poco aclarada, ya que no parece que hay una relación estrecha con la triada clásica de trombogénesis de Virchow, y si con la proximidad anatómica entre las venas y las arterias retinianas. Cuando las paredes de las arterias aumentan de rigidez y grosor comprimen las venas que existen adyacentes compartiendo la vaina adventicia, produciendo un flujo venoso turbulento y aumentando el riesgo de formación de trombo intraluminal. La edad es un factor crucial así como la presencia de hipertensión arterial, siendo la diabetes y la dislipidemia otros factores de riesgo conocidos. También se ha asociado a la hiperhomocisteinemia y el aumento de niveles de anticuerpos anticardiolipinas. Cada vez hay más datos del elevado riesgo de los pacientes con OVR a desarrollar enfermedades cardiovasculares, de ahí la importancia en cuanto a la prevención y control de factores de riesgo cardiovasculares. OBJETIVO: El objetivo principal ha sido analizar los principales factores de riesgo asociados con OVR y compararlos con los presentes en TVP con el fin de intentar discernir en su etiopatogenia. MATERIAL Y MÉTODOS: Se trata de un estudio retrospectivo, observacional realizado en pacientes diagnosticados de oclusión venosa retiniana por métodos objetivos (angiografía con fluoresceína) en el Servicio de Oftalmología del Hospital Clínico Universitario Virgen de la Arrixaca que posteriormente fueron derivados a la consulta monográfica de enfermedad tromboembólica venosa del Servicio de Medicina Interna. Fueron excluidos aquellos pacientes que tuvieran OVR previa. Se estudiaron los factores de riesgo de cada uno de los pacientes así como diferentes variables analíticas que incluían homocisteina y anticuerpos anticardiolipinas. Se compararon los diferentes factores de riesgo y parámetros analíticos con los pacientes diagnosticados de trombosis venosa profunda. RESULTADOS: Se incluyeron 200 pacientes en total (50 con oclusión venosa retiniana y 150 con trombosis venosa profunda). Las variables embarazo/puerperio, antecedente familiar de ETEV, antecedente personal de TVP, tratamiento hormonal activo, anticoagulante lúpico positivo e inmovilización y hospitalización reciente resultaron más frecuentes en pacientes con TVP. Sin embargo, las variables diabetes mellitus, hipertensión arterial y dislipidemia fueron más frecuentes en pacientes con OVR. En cuanto a las variables cuantitativas; la edad, glucosa y colesterol se asociaron más con oclusión venosa retiniana y el fibrinógeno con trombosis venosa profunda. En el análisis multivariado la variable más importante para padecer una TVP es el antecedente de ETEV (OR 11,42 [IC 95% 1,425-91,603]) así como tener un fibrinógeno mayor de 350mg/dl (OR 3,729 [IC 95% 1,71-8,136] siendo este valor el que mayor sensibilidad y especificidad ofrece (sensibilidad: 0,77 y especificidad: 0,46). DISCUSIÓN: La oclusión venosa retiniana es un trastorno vascular retiniano frecuente que ocasiona pérdida de visión y que aumenta claramente con la edad. La patogenia aún se encuentra poco esclarecida aunque cada vez toma más protagonismo la patología arterial. Se relaciona claramente con la edad, la hipertensión arterial así como dislipidemia, diabetes mellitus y tabaquismo. Está claramente asociada con los factores de riesgo cardiovascular y con el desarrollo de enfermedades cardiovasculares, por ello, tiene importancia el seguimiento y control de factores de riesgo en estos pacientes. En nuestro estudio los pacientes con OVR son de mayor edad que los de TVP, así como la hipertensión arterial es más frecuente en OVR en concordancia con lo publicado en la literatura, sin embargo, no hubo significancia estadística (p 0,066). La diabetes mellitus y la dislipidemia fueron más frecuentes en OVR de forma significativa en este grupo (p 0,000 y p 0,022 resepectivamente). De igual manera, la edad, glucosa y colesterol elevados en sangre estuvieron asociados de forma significativa en pacientes con OVR (p 0,001; p 0,001 y p 0,021 respectivamente), mientras que el fibrinógeno elevado estuvo relacionado de forma estadísticamente significativa (p 0,000) con pacientes con trombosis venosa profunda. CONCLUSIONES: Estos resultados refuerzan, por tanto, que la oclusión venosa retiniana tiene mayor relación con los factores de riesgo cardiovascular, con la patología y daño sobre la pared arterial a pesar de que la trombosis se produzca en la vena retiniana, y no parece ser una manifestación distinta de la enfermedad tromboembólica venosa, sino, que podrían tratarse de diferentes entidades clínicas. Por lo tanto, este estudio aclara algo más las diferencias obvias entre los factores de riesgo de ambas patologías y su patogenia, así como, la importancia del papel del médico internista en el control de factores de riesgo de estos pacientes.Medicin

Effect of different morphology of titanium surface on the bone healing in defects filled only with blood clot: a new animal study design

Background. The objective of the present histologic animal study was to analyze whether roughness of the titanium surface can influence and/or stimulate the bone growth in defects filled with the blood using a rabbit tibia model. Materials and Methods. Forty sets (implant and abutment), dental implant (3.5 mm in diameter and 7 mm in length) plus healing abutment (2.5 mm in diameter), were inserted in the tibiae of 10 rabbits. Moreover, twenty titanium discs were prepared. The abutment and discs were treated by 4 different methods and divided into 4 groups: (group A) machined abutments (smooth); (group B) double acid etching treatment; (group C) treatment with blasting with particles of aluminum oxide blasted plus acid conditioning; (group D) treatment with thorough blasting with particles of titanium oxide plus acid conditioning. The discs were used to characterize the surfaces by a profilometer and scanning electronic microscopy. Results. After 8 weeks, the new bone formation around the sets of the samples was analyzed qualitatively and quantitatively in relation to bone height from the base of the implant and presence of osteocytes. Group C (1.50±0.20 mm) and group D (1.62±0.18 mm) showed bone growth on the abutment with higher values compared to group A (0.94±0.30 mm) and group B (1.19±0.23 mm), with significant difference between the groups (P < 0.05). In addition, osteocyte presence was higher in groups with surface treatment related to machined (P < 0.05). Conclusions. Within the limitations of the present study, it was possible to observe that there is a direct relationship between the roughness present on the titanium surface and the stimulus for bone formation, since the presence of larger amounts of osteocytes on SLA surfaces evidenced this fact. Furthermore, the increased formation of bone tissue in height demonstrates that there is an important difference between the physical and chemical methods used for surface treatment

Study of two bovine bone blocks (sintered and non-sintered) used for bone grafts: physico-chemical characterization and in vitro bioactivity and cellular analysis

High-temperature compression and electron backscatter diffraction (EBSD) techniques were used in a systematic investigation of the dynamic recrystallization (DRX) behavior and texture evolution of the Inconel625 alloy. The true stress–true strain curves and the constitutive equation of Inconel625 were obtained at temperatures ranging from 900 to 1200 °C and strain rates of 10, 1, 0.1, and 0.01 s−1. The adiabatic heating effect was observed during the hot compression process. At a high strain rate, as the temperature increased, the grains initially refined and then grew, and the proportion of high-angle grain boundaries increased. The volume fraction of the dynamic recrystallization increased. Most of the grains were randomly distributed and the proportion of recrystallized texture components first increased and then decreased. Complete dynamic recrystallization occurred at 1100 °C, where the recrystallized volume fraction and the random distribution ratios of grains reached a maximum. This study indicated that the dynamic recrystallization mechanism of the Inconel625 alloy at a high strain rate included continuous dynamic recrystallization with subgrain merging and rotation, and discontinuous dynamic recrystallization with bulging grain boundary induced by twinning. The latter mechanism was less dominan

Biomechanical and histological analysis of titanium (machined and treated surface) versus zirconia implant materials: an in vivo animal study

This article belongs to the Special Issue Clinical Implants and the Biocompatibility of Biodegradable BiomaterialsObjectives: The aim of this study was to perform an in vivo histological comparative evaluation of bone formation around titanium (machined and treated surface) and zirconia implants. For the present study were used 50 commercially pure titanium implants grade IV, being that 25 implants with a machined surface (TiM group), 25 implants with a treated surface (TiT group) and, 25 implants were manufactured in pure zirconia (Zr group). The implants (n = 20 per group) were installed in the tibia of 10 rabbits. The implants distribution was randomized (n = 3 implants per tibia). Five implants of each group were analyzed by scanning electron microscopy and an optical laser profilometer for surface roughness characterization. Six weeks after the implantation, 10 implants for each group were removed in counter-torque for analysis of maximum torque value. The remaining samples were processed, included in historesin and cut to obtain non-decalcified slides for histomorphological analyses and histomorphometric measurement of the percentage of bone-implant contact (BIC%). Comparisons were made between the groups using a 5% level of significance (p < 0.05) to assess statistical differences. The results of removal torque values (mean ± standard deviation) showed for the TiM group 15.9 ± 4.18 N cm, for TiT group 27.9 ± 5.15 N cm and for Zr group 11.5 ± 2.92 N cm, with significant statistical difference between the groups (p < 0.0001). However, the BIC% presented similar values for all groups (35.4 ± 4.54 for TiM group, 37.8 ± 4.84 for TiT group and 34.0 ± 6.82 for Zr group), with no statistical differences (p = 0.2171). Within the limitations of the present study, the findings suggest that the quality of the new bone tissue formed around the titanium implants present a superior density (maturation) in comparison to the zirconia implants

Microgrooves and microrugosities in titanium implant surfaces: an in vitro and in vivo evaluation

This article belongs to the Special Issue Clinical Implants and the Biocompatibility of Biodegradable BiomaterialsThe physical characteristics of an implant surface can determine and/or facilitate osseointegration processes. In this sense, a new implant surface with microgrooves associated with plus double acid treatment to generate roughness was evaluated and compared in vitro and in vivo with a non-treated (smooth) and double acid surface treatment. Thirty disks and thirty-six conical implants manufactured from commercially pure titanium (grade IV) were prepared for this study. Three groups were determined, as described below: Group 1 (G1), where the samples were only machined; group 2 (G2), where the samples were machined and had their surface treated to generate roughness; and test group 3 (G3), where the samples were machined with microgrooves and the surface was treated to generate the roughness. For the in vitro analysis, the samples were submitted to scanning microscopy (SEM), surface profilometry, the atomic force microscope (MFA) and the surface energy test. For the in vivo analyses, thirty-six implants were placed in the tibia of 9 New Zealand rabbits in a randomized manner, after histological and histomorphometric analysis, to determine the level of contact between the bone and implant (BIC%) and the bone area fraction occupancy (BAFO%) inside of the threads. The data collected were statistically analyzed between groups (p < 0.05). The in vitro evaluations showed different roughness patterns between the groups, and the G3 group had the highest values. In vivo evaluations of the BIC% showed 50.45 ± 9.57% for the G1 group, 55.32 ± 10.31% for the G2 group and 68.65 ± 9.98% for the G3 group, with significant statistical difference between the groups (p < 0.0001). In the BAFO% values, the G1 group presented 54.97 ± 9.56%, the G2 group 59.09 ± 10.13% and the G3 group 70.12 ± 11.07%, with statistical difference between the groups (p < 0.001). The results obtained in the evaluations show that the surface with microgrooves stimulates the process of osseointegration, accelerating the healing process, increasing the contact between the bone and the implant and the area of new bone formation

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Analysis of Trauma Intensity during Surgical Bone Procedures Using NF-κB Expression Levels as a Stress Sensor: An Experimental Study in a Wistar Rat Model

Aim and objectives: It is well known that the transcription factor NF-&#954;B regulates multiple aspects of innate and adaptive immune functions and functions as a pivotal mediator of inflammatory responses. In the present study, we evaluated the trauma generated (inflammatory reaction) after osteotomy bone surgical procedures and placement of implants in the femoral cortical bone of Wistar rats. Surgical stress was evaluated measuring the release and activation of the NF-&#954;B factor. Materials and Methods: Rats were divided into four groups (n = 10) and submitted to different surgical treatments: Control Group (G1 group), only bone perforation was performed without irrigation; Implant Group (G2 group), a titanium implant was inserted after bone perforation without irrigation; Irrigated Group (G3 group) perforations were performed with intense irrigation; and Vitaminic Compound Group (G4 group) surgical perforation was performed without irrigation and a vitaminic compound containing the principal ions present in the natural bone structure was used to fill the bone defect. All animals were euthanized six hours after the surgical procedure and NF-&#954;B levels were determined through immunohistochemical stain followed by direct counting of labeled and unlabeled osteocytes. Results: Among different treated groups, the overall mean of the NF-&#954;B positive cell count in all positions were higher for G1 group (33.4 &#177; 2.45 cells). NF-&#954;B values were lower in the G2 group (28.9 &#177; 2.70 cells), whereas in the G3 group (24.3 &#177; 2.72 cells) as well as in G4 group still lesser NF-&#954;B positive cells were counted (26.5 &#177; 2.60 cells). Conclusions: The results here presented suggest that maneuvers performed during osteotomy procedures can significantly affect inflammation levels. The NF-&#954;B activation during the surgical procedures can be minimized and/or controlled thought the adequate irrigation or application of adequate substances

Implementación del sistema de gestión del riesgo biológico en la Universidad Médica de Villa Clara Implementation of the biological risk management system in the Medical University of Villa Clara

Introducción: para cumplir lo que está establecido legalmente en Cuba, la Universidad de Ciencias Médicas de Villa Clara ha incorporado los aspectos relacionados con la seguridad biológica en sus programas de investigación y desarrollo, inspecciones, inversiones y regulaciones internas, para lo que ha destinado los recursos necesarios y ha promovido la realización de investigaciones puras en esta materia. En consecuencia, el propósito del presente trabajo es desarrollar e implementar el sistema de gestión del riesgo biológico en esta Universidad Médica. Métodos: el estudio comprendió varias etapas: identificación, evaluación y gestión del riesgo. Las primeras dos etapas constituyeron el diagnóstico del estado de seguridad biológica de cada área y del centro, para lo que se empleó el análisis documental, se efectuaron entrevistas a decisores y fue aplicado un cuestionario a una muestra representativa de trabajadores de cada una de las áreas. En la tercera etapa se diseñó el sistema de gestión del riesgo biológico, el cual fue sometido a su evaluación por los expertos que participaron en la investigación. Resultados: se realizó el diagnóstico y se encontraron dificultades en las áreas expuestas con respecto a la documentación necesaria y al estado de conocimiento y aplicación práctica de los requerimientos de bioseguridad; también, como resultado del diagnóstico, se identificó el grupo de riesgo en las áreas estudiadas. Se diseñó e implementó el sistema basado en las estrategias de formación de recursos humanos, de identificación y de gestión de recursos económicos y financieros, y de establecimiento de los requisitos de diseño de esta Universidad. Conclusión: Este sistema ha permitido la implementación de los requisitos establecidos en la legislación de una forma orgánica y de mejora continua, y se ha dirigido, además, al alcance de un adecuado y óptimo desempeño ambiental y de esta materia en nuestra Universidad Médica.Introduction: To complete what is established legally in our country, Medical Sciences University of Villa Clara has incorporated the aspects related with the biosafety in its investigation and development programs, inspections, investments and internal regulations, dedicating the necessary resources for it and promoting the perform of pure investigations in this matter. In consequence, the purpose of the present work is to develop and to implement a biological risk management system in this Medical University. Methods: The study involved several stages: identification, evaluation and management of the risk. The first two stages constituted the diagnosis of the biosafety state of each area and the Center; the methods used for its development were: documental analysis, interviews to manager and questionnaire to a representative sample of workers of each area. In the third stage the biological risk management system was designed and subjected to its evaluation for the experts that participated in the investigation. Results: it was carried out the diagnosis and it were found difficulties in exposed areas in regard to the necessary documentation and to the state of knowledge and practical application of the biosafety requirements; also, as a result of the diagnosis, the group of risk (II) was identified in the studied areas. It was designed and it implemented the system based on the strategies that involves human resources formation, identification and management of economic and financial resources, and of establishment of the design requirements of this University. This system has allowed the implementation of the requirements settled down in the legislation, in an organic way with continuous improvement; it has reached an appropriate environmental performance of this matter in our Medical University