Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

Minimal invasive surgical resection of myxomas: a three case series study / Resección quirúrgica mínimamente invasiva de mixomas: estudio de tres casos

Abstract Introduction and Objective Cardiac tumors are often unrecognized until autopsies are performed or diagnosed from routine studies based on unspecific symptoms. The most common type of tumor is the myxoma, although rare, upon diagnosis an urgent surgical resection is often required. Previously the ideal surgical approach was a standard median sternotomy, however recently newer surgical techniques have been employed with excellent results. We describe a recent surgical approach via the right lateral minithoracotomy as a minimally invasive intervention with three cases that evidence an appropriate and ideal surgical approach. Method and Patients We present three cases of minimally invasive myxoma resection via the right lateral minithoracotomy. Results and discussion In this three-case series study, no complications were reported peri-operatively nor at the 6 and 12-month follow-ups. In comparison with international literature, surgical approaches in Colombia are comparable with successful resection and little or no complications peri-operatively. Conclusions The right lateral minithoracotomy appears to be a safe approach in myxoma resection. We hope to enhance and promote the surgical community in Colombia to opt for alternative less invasive approaches in these type of cases, to ensure excellent results and promote further research as seen in other countries.

Resumen Introducción y Objetivo Los tumores cardíacos no suelen ser diagnosticados hasta la realización de autopsia o en otros casos como hallazgos incidentales. El tumor cardiaco más común es el mixoma, aunque es poco frecuente; en el momento del diagnóstico a menudo se requiere una resección quirúrgica urgente. Anteriormente el enfoque quirúrgico era una atriotomía abierta derecha; sin embargo, recientemente se han empleado técnicas quirúrgicas nuevas con excelentes resultados. Describimos una técnica quirúrgica reciente a través de la minitoracotomía lateral derecha como un método mínimamente invasivo con tres casos que evidencian un método quirúrgico apropiado e ideal. Métodos y pacientes: Se presentan tres casos de resección mínimamente invasiva de mixomas a través de una minitoracotomía lateral derecha. Resultados y discusión: Es estos tres casos no se reportaron complicaciones perioperatorias ni durante el seguimiento a los 6 y 12 meses. En comparación con otras series de casos en la literatura, el enfoque en Colombia ha sido comparable tanto en los resultados exitosos como con las técnicas quirúrgicas, sin complicaciones asociadas. Conclusiones La minitoracotomía lateral derecha puede ser considerada segura en resección de mixoma. Con este tipo de reportes se espera suscitar en la comunidad médica la elección de alternativas quirúrgicas mínimamente invasivas para garantizar excelentes resultados y promover la investigación, como se evidencia en el resto del mundo.

Immunoglobulin G4-related gastric pseudotumor - An impostor: Case report.

INTRODUCTION: Gastric pseudotumors are rare entities whose clinical presentation resembles typical gastric neoplasias, often making them unrecognized unless other causes are considered. PRESENTATION OF CASE: We present a case report of a patient that debuts with dysphagia, with an abdominal computed axial tomography (CAT) scan revealing a mass at the gastro-esophageal junction suggestive of malignant origin, with studies revealing it to be Immunoglobulin G4-related (IgG4). DISCUSSION: The diagnosis and identification of IgG4-related gastric pseudotumors is very complicated, often and most commonly an incidental diagnosis upon histologic analysis, as is the situation in this case. CONCLUSION: Understanding its clinical course and early diagnosis can reduce unwarranted surgical intervention in some patients with IgG4-related disease.

Left diaphragmatic hernia following thoracoabdominal aortic repair: A case report.

INTRODUCTION: Diaphragmatic hernias are somewhat rare complications of thoracoabdominal interventions. Given their late clinical manifestations and misdiagnosis, their incidence is unknown. These hernias have a high mortality risk when an emergency intervention is warranted due to complications from visceral strangulation. CASE PRESENTATION: We present the case of a 67-year-old male with prior history of thoracoabdominal aortic repair, who reconsults due to upper gastrointestinal bleeding. Upon arrival, imaging shows a left diaphragmatic herniation with migration of the stomach, omentum and spleen to the thoracic cavity. Through laparoscopic approach, a left diaphragmatic hernial defect is identified with protrusion of half the stomach, omentum and the posterior aspect of the spleen with a sub capsular tear. Additionally, a severe adhesion syndrome on the chest wall and diaphragm were also evident, with entrapment of the inferior lobe of the left lung. The contents were successfully reduced, however pulmonary decortication and extensive adhesiolysis through thoracoscopy was required for complete extraction, enabling a primary repair without tension. CONCLUSIONS: We present an infrequent pathology without an established incidence, which has relevant clinical and surgical implications at any level of care, in this case requiring interdisciplinary management. The suspicion of diaphragmatic hernia in a patient with past medical history of thoracoabdominal aortic repair with non-specific gastrointestinal symptoms is essential. We emphasize the importance of clinical suspicion of this complication once the surgical precedent has been identified.

Total gastrectomy in systemic scleroderma when anti-reflux surgery is not viable: A case report.

INTRODUCTION: Systemic scleroderma is an autoimmune disease that can affect the respiratory system and the gastrointestinal tract. When diffuse lung disease and pulmonary hypertension develop, a lung transplant is usually considered as treatment. This option, however, is not feasible in the presence of concomitant gastroesophageal reflux disease. In this case, medical therapy is initially warranted. If this fails, surgical approach may be considered in order for the patient to be a lung transplant candidate. CASE PRESENTATION: A 56-year-old female, with previous history of intestinal pneumonitis, mild pulmonary hypertension and gastroesophageal reflux secondary to systemic scleroderma, is considered for lung transplant. Initially, due to persistent gastroesophageal reflux, a transplant was not a viable. This was corrected with an open gastrectomy with roux-en-Y anastomosis. Follow-up one week later revealed normal anatomy, adequate esophageal-jejunal anastomosis, and adequate contrast medium transit via esophagogram. Additionally, there was no evidence of contrast medium reflux indicating a resolved gastroesophageal reflux disease. This led to the patient becoming a candidate for lung transplant. DISCUSSION: We suggest an open gastrectomy with roux-en-Y anastomosis as an alternative to the Nissen fundoplication for patients with connective tissue disease that develop terminal pulmonary consequences and require a lung transplant.

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity.

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma.

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 µg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

Pneumoperitoneum, pneumatosis intestinalis and portal venous gas: Rare gastrostomy complications case report.

INTRODUCTION: The gastrostomy is one of the most common procedures performed in general surgery. Although a simple procedure, it is not exempted from potential complications, specifically portal venous gas and intestinal pneumatosis being some of the ones with higher rates of mortality. The following case report presents a pneumoperitoneum due to extensive pneumatosis from esophageal, gastric, intestinal and portal gas. These rare complications were managed medically without undergoing emergency surgical intervention. PRESENTATION OF CASE: A 19-year-old male patient, with previous history of cerebral palsy, chronic malnutrition and severe physical deconditioning, required a nutritional access. Due to co-existing pathologies, an open gastrostomy was chosen as the best intervention, which was performed without complications. On the tenth postoperative day, patient presents abdominal pain and diarrhea; laboratory results were within normal limits, and the abdominal computed tomography scan reported extensive pneumatosis compromising esophagus, stomach, small intestine, part of the colon, pneumoperitoneum and gas in the portal venous system. Medical management was carried out with an adequate recovery. DISCUSSION: Intestinal pneumatosis and portal venous gas are rare and potentially lethal complications. Surgical intervention as well as severe malnutrition impairs carbohydrate digestion and promotes bacterial fermentation forming large volumes of gas and dissection of the intestinal mucosal wall, causing the intestinal pneumatosis evidenced in this case report. CONCLUSIONS: This case report presents a rare open gastrostomy complication, as well as a differential diagnosis to pneumoperitoneum. Additionally, the medical management poses a successful alternative to an emergency surgical intervention.

Proliferative Properties of 17ß-aminoestrogens in MCF-7 Human Breast Cancer Cells.

The 17ß-aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E2 ) which presents pro-coagulant effects, potentially thrombogenic. They possess anti-anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF-7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs' proliferation properties were evaluated compared with E2 in MCF-7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co-incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERß). E2 and AEs increased MCF-7 cell proliferation; their proliferative effect was between 1.5-2 and E2 = 3.6 compared with controls (0); their relative proliferative effect was 18-38% (E2 = 100%) with a relative proliferative potency of 4.5-8.9 (E2 = 100). The ERα antagonist MPP inhibited the MCF-7 cell proliferation induced by E2 and AEs; on the contrary, the ERß antagonist PHTPP exacerbated the proliferative response, showing that the AEs' proliferative activity was mainly ERα-mediated and apparently controlled by ERß. Preliminary cytometric DNA flow analysis showed that AEs' cell cycle S phase inducer property was lower than E2 following the proliferative order: E2 > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.

Benefits of a Culturally Tailored Health Promotion Program for Latino Youth With Disabilities and Their Families.

Little research is available about youth with disabilities, who experience numerous inequalities in health outcomes compared with youth without disabilities. Youth with disabilities experience many environmental and attitudinal barriers in maintaining healthy lifestyles, which put them at risk for obesity. Strong evidence has suggested that obesity rates are higher among youth with disabilities than among their nondisabled peers. The purpose of this study was to implement and examine the benefits of a culturally tailored healthy lifestyles program for Latino youth with disabilities and their families. Several cultural adaptations were made to align with the target population's cultural norms. Seventeen Latino families identified 67 behaviors they wanted to change or new habits they wanted to establish. The postassessment data showed that several family routines improved, and families reported engaging in many of the healthy habits they had identified for themselves. Implications of culturally appropriate and accessible programming are discussed.

Biopsia de ganglio centinela en cáncer de mama después de neoadyuvancia en una población latinoamericana / Sentinel Node Biopsy in Breast Cancer After Neoadjuvant Therapy in a Latin-American population

Objetivo: Determinar la utilidad de la biopsia del ganglio centinela en cáncer de mama después neoadyuvancia. Método: Estudio de prueba diagnóstica. Resultados: El análisis se lleva a cabo en 67 pacientes intervenidas en el Instituto Nacional de Cancerología (INC) (Bogotá, Colombia), la obtención de una tasa de migración axilar de 85%. La tasa de identificación del ganglio centinela fue del 90%. La tasa de falsos negativos fue del 25%. El rendimiento de la prueba de diagnóstico muestra: una sensibilidad del 75%; una especificidad de 100%; un valor predictivo positivo de 100%; un valor predictivo negativo de 77,5% y un valor de precisión de 85,6%. Conclusiones: Según los resultados de nuestra serie, esta técnica no se recomienda como procedimiento estándar aún en pacientes con axila clínicamente negativa corroborada con ecografía axilar. El alto porcentaje de falsos negativos (25%) encontrado puede deberse al número elevado de pacientes con estadios localmente avanzados en nuestra serie.

Objective: To determine the usefulness of sentinel node biopsy in breast cancer after neoadjuvant treatment. Methods: A study of a diagnostic test. Results: The analysis was carried out on 67 Latin-American patients treated in the Instituto Nacional de Cancerología (Bogotá, Colombia), obtaining an axillary migration rate of 85%. The sentinel node identification rate was 90%. The false negative rate is 25%. The performance of the diagnostic test shows a sensitivity of 75%, specifity of 100%, positive predictive value of 100%, negative predictive value of 77.5%, and 85.6% accuracy. Conclusions: The results of our study show that this technique is not recommended as standard procedure, even in patients with clinically negative axilla confirmed by axillary ultrasound. The high percentage of false negatives may be due to the high number of patients with locally advanced disease in our series.

Imágenes de resonancia magnética como demostración de recurrencia de cáncer de seno posterior a mastectomía radical y reconstrucción con colgajo músculo-cutáneo transverso de recto abdominal: presentación de caso / Magnetic resonance imaging in the evaluation of recurrent breast cancer after radical mastectomy and transverse rectus abdominis musculocutaneous flap reconstruction: case report

La reconstrucción con colgajo TRAM (colgajo musculo-cutáneo transverso de recto abdominal) es una técnica quirúrgica ampliamente utilizada en pacientes que han sido sometidas a mastectomía radical. La recurrencia local de cáncer de seno se debe al tejido glandular remanente posterior a la mastectomía; su incidencia varía entre 3,8% y 10,6%, dependiendo del estadio de la enfermedad inicial, el subtipo histológico y su comportamiento biológico. Estas recurrencias pueden ser detectadas mediante el examen físico e imágenes diagnósticas, dentro de las cuales la resonancia magnética es la modalidad que ofrece la mejor diferenciación entre cambios posquirúrgicos esperados y recurrencias; sin embargo no se ha establecido un protocolo de seguimiento para estas pacientes. En este artículo se presenta un caso y se revisan las características imaginológicas propias de la reconstrucción como de una recidiva tumoral.

Evaluación de un método de cálculo para estimar la carga de trabajo en trabajadores expuestos a condiciones térmicas extremas / Evaluation of a calculation method for estimating work load in workers exposed to thermal stress

La estimación de la carga de trabajo es un problema central cuando se debe determinar el tiempo de trabajo y la distribución de tareas en el diseño de un sistema de trabajo. Para ello, se requiere contar con herramientas que permitan realizar una evaluación rápida y objetiva con el fin de establecer períodos de trabajo y de reposo de los trabajadores -carga de trabajo- en entornos industriales. En esta investigación se usó como eje central de estudio la actividad de los trabajadores utilizando la metodología de los actogramas analíticos de la acción, el registro de datos se realiza con la ayuda del software Kronos, y para la estimación de la carga de trabajo se modificó la ecuación para el cálculo de la tasa metabólica media presentada en los TLV`s y la guía de seguridad: exposition professionnelle à la chaleur, finalmente para determinar el índice de confort térmico se tomó como referencia los índices de estrés térmico y los índices de exigencia térmica desarrollados por Malchaire (1986). Los resultados del estudio permiten establecer la necesidad del uso de un modelo de cálculo que integre las diversas variables (estructura de las tareas y actividades, tiempo efectivo de exposición, índice WBGT). El modelo de análisis desarrollado permite determinar la carga de trabajo. Sin embargo, se debe tomar en cuenta que la estimación de la carga de trabajo requiere una correcta identificación de la relación entre la situación de trabajo y las exigencias de orden fisiológico en el trabajo. Aplicación industrial: el método desarrollado en este estudio es un instrumento fiable y válido para evaluar la carga de trabajo físico para las condiciones de estrés térmico.

Accurate estimation of physical load represents a challenge when determining optimal working times and distribution of tasks in work system design. Tools that allow a rapid and objective evaluation, for the purpose of establishing adequate work-rest cycles, are needed in industrial environments. In this study, worker activity was measured through the use of action analytical actigrams, aided by Kronos data logging software. For estimation of physical work load we used a modified equation based on the average metabolic rate calculation described in the TLV booklet and on the safety guide "Exposition professionnelle à la chaleur". Calculation of the thermal comfort index was based on the thermal stress and thermal demands indices developed by Malchaire (1986). Results from this study establish that physical work load estimation requires the use of a model that calculates and integrates several variables (tasks and activities structure, effective time of exposure, and WBGT index). The analytical method used allows estimation of physical work load. However, it should be recognized that physical work load estimation requires the correct identification and understanding of the relationships between work conditions and the physiological demands of the job. Industrial application: the method developed in this study represents a reliable and valid tool for assessing physical work load under conditions of thermal stress.

El análisis ergonómico y las lesiones de espalda en sistemas de producción flexible / The Ergonomic Analysis and Back Injuries in Flexible Production System

La identificación y diagnóstico de las lesiones de espalda en la transición del modelo de Taylor al modelo flexible de organización de la producción demanda la intervención, en paralelo, de los diferentes actores de la prevención en el trabajo. Este estudio integra tres modelos de intervención (análisis estructurado de la acción, cuestionarios de síntomas osteomusculares y evaluación osteomuscular) para actividades de trabajo en una planta de envasado y empaque. En este estudio participan 72 trabajadores operativos (a 28 de ellos se les practicó una evaluación osteomuscular). En un periodo de diez meses de intervención se evalúan los componentes físico, cognitivo, organizacional y la dinámica del proceso productivo, desde la óptica de las exigencias osteomusculares. Las diferencias establecidas entre exposición objetiva a riesgo, percepción y apreciación de riesgo de lesión de espalda y evaluación objetiva del estado de la columna, en pre- y postintervención determinan la estructura de un sistema de manejo del riesgo osteomuscular.Este estudio expone que los síntomas de lesión de espalda pueden reducirse de manera eficiente en trabajadores operativos, al combinar medidas que registren el ajuste entre la dinámica, los cambios en el trabajo y el desarrollo de gestos eficientes. Relevancia de este estudio: Los resultados de este estudio pueden aplicarse para prevenir lesiones de espalda en trabajadores de procesos de producción flexible.

Back injuries identification and diagnoses in the transition of the Taylor model to the flexiblemodel of production organization, demands a parallel intervention of prevention actors at work. This study uses simultaneously three intervention models (structured action analysis, muscle skeletal symptoms questionnaires and muscle skeletal assessment) for work activities in a packaging plant. In this study seventy and two (72) operative workers participated (28 workers with muscle skeletal evaluation). In an intervention period of 10 months, the physical, cognitive, organizational components and productive process dynamics were evaluated from the muscle skeletal demands issues. The differences established between objective exposure at risk, back injury risk perception, appreciation and a vertebral spine evaluation, in prior and post intervention, determines the structure for a muscle skeletal risk management system. This study explains that back injury symptoms can be more efficiently reduced among operative workers combining measures registered and the adjustment between dynamics, the changes at work and efficient gestures development. Relevance: the results of this study can be used to prevent back injuries in workers of flexible production processes.

Cáncer de seno y hormonoterapia. Estado actual / Breast cancer and hormone therapy. Current state of knowledge

El manejo del cáncer de seno es multidisciplinario e involucra la cirugía, la quimioterapia, la radioterapia y la hormonoterapia. La hormonoterapia es un tratamiento muy antiguo para el manejo efectivo del cáncer de seno hormono-sensible. Cerca de 75 porciento de las pacientes expresan receptores hormonales en el tumor y el estándar de manejo ha sido con antiestrógenos como el tamoxifeno, que se viene usando desde hace más de 25 años en ensayos clínicos con buena respuesta, mejorando la supervivencia libre de enfermedad (SLE) y la supervivencia total (ST) de las pacientes, tanto en mujeres premenopáusicas como postmenopáusicas; por los efectos secundarios sobre endometrio y coagulación, se han venido desarrollando nuevas drogas llamadas inhibidores de aromatasa, que han sido comparados con el tamoxifeno en el estado metastásico y en adyuvancia, con mejores resultados de supervivencia libre de enfermedad con menos efectos secundarios sobre endometrio y menos eventos trombóticos, aunque aumentan el riesgo de osteoporosis y fracturas con su uso prolongado.

4-Hydroxycoumarin disorganizes the actin cytoskeleton in B16-F10 melanoma cells but not in B82 fibroblasts, decreasing their adhesion to extracellular matrix proteins and motility.

This study determined the in vitro effects of 4-hydroxycoumarin (4-HC) employing the melanoma cell line B16-F10 and the non-malignant fibroblastic cell line B82. 4-HC disorganized the actin cytoskeleton in B16-F10 cells, but not in B82 fibroblasts. Cytoskeletal disorganization correlated with reductions in cell adhesion to four extracellular matrix proteins and inhibition of random motility. 4-HC did not modify cell viability or actin expression, but decreased tyrosine phosphorylation of several proteins in melanoma cells. Because adhesion of tumor cells to extracellular matrix is required during the metastatic process, 4-HC might be useful as an adjuvant therapy for melanoma.

[Response to thymectomy in patients with thymoma]. / Respuesta a la timectomía en pacientes con timoma y miastenia gravis.

INTRODUCTION: Approximately 10% of patients with myasthenia gravis also have thymomas. The objective of this study was to describe the evolution after the thymectomy in 10 cases of myasthenia gravis associated with thymomas. METHODS: The study was based in a cohort of 132 patients with the diagnosis of myasthenia gravis, that underwent thymectomy between 1987 and 1997, and had at least three years of follow-up. We found 10 cases (7%) of thymomas. We analyzed the following variables: sex, age, associated diseases, disease evolution, Osserman, dose of edrophonium before surgery, steroid use before surgery, types of thymectomy, Osserman after surgery, pathology findings, and evolution. We used descriptive statistics according to the measurement level of the variables. RESULTS: Four (40%) were women and 6 (60%) were men. The antibodies against the acetylcholine receptor were tested in only 5 (50%) patients, and in all of them they were positive. 4 (40%) patients had complications after the thymectomy, being 2 (20%) of them myasthenic crisis, one (10%) pneumonia and another (10%) hemorrhage in the surgical wound. Six (60%) cases had malignant thymomas and 4 (40%) were benign. In the follow-up, 4 (40%) patients had a good clinical response of myasthenia gravis and 6 (60%) had no changes. CONCLUSION: The response to thymectomy was not as good as the response of the vast majority of patients with myasthenia gravis without thymomas. We found a high frequency of malignant thymomas in our patients.

Anormalidades en el sistema adhesivo de neoplasias pulmonares / Abnormalities in adhesión system of pulmonary neoplasms

La progresión de una neoplasia pulmonar requiere alteraciones en la expresión de moléculas de adhesión en la célula tumoral. Un decremento en la expresión de E-cadherina y de las cateninas a y b disminuye la adhesión homotípica e incrementa el número de células neoplásicas liberadas del tumor primario. Las integrinas presentan cambios complejos en su expresión; la capacidad invasiva se ve favorecida por el aumento en la expresión de unas integrinas, como la a 2b 1 y por la disminución en la expresión de otras, como la a 3b 1. Los cambios en la expresión de ICAM-1 favorecen la evasión de la respuesta inmune. La disminución en la densidad de ICAM-1 en la superficie de células tumorales disminuye la posibilidad de contacto célula-célula. El aumento en la concentración de la isoforma soluble de ICAM-1 bloquea los contrarreceptores presentes en las células inmunológicas. También se han identificado alteraciones en moléculas que modulan la adhesión, como FAK y paxilina. Las moléculas de adhesión y los componentes regulatorios de la adhesión, pueden ser blancos farmacológicos para el desarrollo de nuevas terapias adyuvantes para el tratamiento del cáncer.