Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Visualization in 2D/3D registration matters for assuring technology-assisted image-guided surgery.

PURPOSE: Image-guided navigation and surgical robotics are the next frontiers of minimally invasive surgery. Assuring safety in high-stakes clinical environments is critical for their deployment. 2D/3D registration is an essential, enabling algorithm for most of these systems, as it provides spatial alignment of preoperative data with intraoperative images. While these algorithms have been studied widely, there is a need for verification methods to enable human stakeholders to assess and either approve or reject registration results to ensure safe operation. METHODS: To address the verification problem from the perspective of human perception, we develop novel visualization paradigms and use a sampling method based on approximate posterior distribution to simulate registration offsets. We then conduct a user study with 22 participants to investigate how different visualization paradigms (Neutral, Attention-Guiding, Correspondence-Suggesting) affect human performance in evaluating the simulated 2D/3D registration results using 12 pelvic fluoroscopy images. RESULTS: All three visualization paradigms allow users to perform better than random guessing to differentiate between offsets of varying magnitude. The novel paradigms show better performance than the neutral paradigm when using an absolute threshold to differentiate acceptable and unacceptable registrations (highest accuracy: Correspondence-Suggesting (65.1%), highest F1 score: Attention-Guiding (65.7%)), as well as when using a paradigm-specific threshold for the same discrimination (highest accuracy: Attention-Guiding (70.4%), highest F1 score: Corresponding-Suggesting (65.0%)). CONCLUSION: This study demonstrates that visualization paradigms do affect the human-based assessment of 2D/3D registration errors. However, further exploration is needed to understand this effect better and develop more effective methods to assure accuracy. This research serves as a crucial step toward enhanced surgical autonomy and safety assurance in technology-assisted image-guided surgery.

Direct Gene Expression Profile Prediction for Uveal Melanoma from Digital Cytopathology Images via Deep Learning and Salient Image Region Identification.

Objective: To demonstrate that deep learning (DL) methods can produce robust prediction of gene expression profile (GEP) in uveal melanoma (UM) based on digital cytopathology images. Design: Evaluation of a diagnostic test or technology. Subjects Participants and Controls: Deidentified smeared cytology slides stained with hematoxylin and eosin obtained from a fine needle aspirated from UM. Methods: Digital whole-slide images were generated by fine-needle aspiration biopsies of UM tumors that underwent GEP testing. A multistage DL system was developed with automatic region-of-interest (ROI) extraction from digital cytopathology images, an attention-based neural network, ROI feature aggregation, and slide-level data augmentation. Main Outcome Measures: The ability of our DL system in predicting GEP on a slide (patient) level. Data were partitioned at the patient level (73% training; 27% testing). Results: In total, our study included 89 whole-slide images from 82 patients and 121 388 unique ROIs. The testing set included 24 slides from 24 patients (12 class 1 tumors; 12 class 2 tumors; 1 slide per patient). Our DL system for GEP prediction achieved an area under the receiver operating characteristic curve of 0.944, an accuracy of 91.7%, a sensitivity of 91.7%, and a specificity of 91.7% on a slide-level analysis. The incorporation of slide-level feature aggregation and data augmentation produced a more predictive DL model (P = 0.0031). Conclusions: Our current work established a complete pipeline for GEP prediction in UM tumors: from automatic ROI extraction from digital cytopathology whole-slide images to slide-level predictions. Our DL system demonstrated robust performance and, if validated prospectively, could serve as an image-based alternative to GEP testing.

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Multicenter lupus register from Argentina, the RELESSAR database: Influence of ethnicity on disease phenotype.

OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

QU-BraTS: MICCAI BraTS 2020 Challenge on Quantifying Uncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS.

"Malignant" origin of the left coronary artery, case report / Origen «maligno¼ de arteria coronaria izquierda, reporte de caso

Anomalous origin of the coronary arteries are very infrequent, however their diagnosis has been increasing due to the increase in the use of coronary computer tomography angiography (CCTA) within the algorithm of patients with suspected coronary disease; We present a case of a patient with acute on chronic chest pain in whom an anomalous origin was diagnosed with an interarterial "malignant" course of the left coronary artery, who was taken to surgery with complete improvement of symptoms and quality of life.

El origen anómalo de las arterias coronarias (OAAC) es muy infrecuente, sin embargo, su diagnóstico ha ido en aumento por el incremento en el uso de la angiotomografía coronaria por tomografía dentro del algoritmo del paciente con sospecha de enfermedad coronaria. Presentamos el caso de un paciente con dolor torácico crónico agudizado en quien se diagnosticó un OAAC de la coronaria izquierda con curso interarterial «maligno¼, que fue llevado a cirugía, con mejoría completa de síntomas y en calidad de vida.

Acoplamiento molecular y modelado tridimensional por homología de flavonoides derivados de amentoflavona con las neuraminidasas H1N1 y H5N1 del virus de gripe aviar / Molecular docking and threedimensional homology modeling of flavonoids derived from amentoflavone with H1N1 and H5N1 neuraminidases of avian influenza virus / Modelagem de homologia tridimensional e de acoplamento molecular de flavonóides derivados de amentoflavona com as neuraminidases H1N1 e H5N1 do vírus da gripe aviária

Resumen El virus de la influenza A es el responsable de la gripe aviar, condición patológica que afecta principalmente aves, caballos y mamíferos marinos, sin embargo, el subtipo H5NI tiene la capacidad de infectar a los humanos de forma rápida, exponiéndolos a un posible evento pandémico. Por tanto, el objetivo de este estudio fue realizar el acoplamiento molecular y modelado tridimensional por homología de flavonoides derivados de amentoflavona con las neuraminidasas H1N1 y H5N1 del virus de gripe aviar. Inicialmente, se obtuvo por homología la estructura 3D de la neuraminidasa H1N1. Seguido, se realizó un acoplamiento molecular de H1N1 con seis ligandos (F36, Ginkgetin, 3S,3R, 5S,5R, 6S y 6R), y más adelante H5N1 y los ligandos F36, Ginkgetin, 5R y 6R. Finalmente, a los complejos obtenidos se les realizó un análisis de interacciones. Los resultados dejaron en evidencia una relación entre la actividad inhibitoria y las interacciones tipo puente de hidrógeno e hidrofóbicas formadas entre el sitio activo de las neuraminidasas y los ligandos. Además, se observó una mejora en la actividad inhibitoria de los ligandos para la estereoquímica tipo R y sustituyentes poco voluminosos. De ahí que se propongan la evaluación experimental de los ligandos 5R y 6R como potenciales inhibidores de H5N1.

Abstract The influenza A virus is responsible for bird flu; a pathological condition that mainly affects birds, horses, and marine mammals, however, the H5N' subtype can infect humans quickly; exposing them to a possible pandemic event. Therefore, the objective of this study was to carry out the molecular docking and three-dimensional homology modeling of flavonoids derived from amentoflavone with H'NI and H5NI neuraminidases of the avian influenza virus. Initially, the 3D structure of H1N1 neuraminidase was obtained by homology. Then, the molecular docking of H1N1 was carried out with six ligands (F36, Ginkgetin, 3S, 3R, 5S, 5R, 6S, and 6R), and subsequently H5N1 and F36, Ginkgetin, 5R, and 6R ligands. Finally, an interaction analysis of the proteinligand complex was performed. The results showed a relationship between the inhibitory activity of ligands and the hydrophobic and hydrogen bridge-type interactions. In addition, an improvement in the inhibitory activity of the ligands for R-type stereochemistry and small bulky substituents was observed. Thus, the experimental evaluation of the 5R and 6R ligands as potential H5N' inhibitors is proposed.

Resumo O vírus influenza A é responsável pela gripe aviária; condição patológica que afeta principalmente pássaros, cavalos e mamíferos marinhos, no entanto, o subtipo H5N' tem a capacidade de infectar humanos rapidamente; assim, expondo-os a um possível evento pandémico. Portanto, o objetivo deste estudo foi realizar o acoplamento e modelagem de homologia tridimensional de flavonóides derivados da amentoflavona com as neuraminidases H1N1 e H5N1 do vírus da influenza aviária. Inicialmente, a estrutura 3D da neuraminidase H1N1 foi obtida por homologia. Em seguida, o acoplamento molecular de H1N1 foi realizado com seis ligantes (F36, Ginkgetin, 3S, 3R, 5S, 5R, 6S e 6R) e, posteriormente, H5NI e os ligantes F36, Ginkgetin, 5R e 6R. Finalmente, uma análise de interação foi realizada nos complexos obtidos. Os resultados mostraram uma relação entre a atividade inibitória e as interações hidrofóbicas e do tipo ponte de hidrogénio formadas entre o sítio ativo das neuraminidases e os ligantes. Além disso, foi observada uma melhoria na atividade inibitória dos ligantes para a estereoquímica do tipo R e pequenos substituintes volumosos. Assim, é proposta a avaliação experimental dos ligantes 5R e 6R como potenciais inibidores do H5NI.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

Alteración en la expresión de proteínas transportadoras de colesterol y moléculas inmunomoduladoras en pacientes con VIH-1 / Altered expression of cholesterol transport proteins and immunomodulators molecules in HIV-1 infected patients

Debido a que la terapia antirretroviral no logra controlar la activación inmune asociada a la infección por VIH-1, el estudio de moléculas inmunomoduladoras puede proporcionar alternativas para su control. En este sentido, el propósito de este estudio fue evaluar la expresión transcripcional de moléculas asociadas con el metabolismo del colesterol-HDL (C-HDL) y con la respuesta inflamatoria mediada por el inflamasoma NLRP3 en pacientes infectados con VIH-1. En este estudio transversal, se incluyeron 23 pacientes VIH-1 sin tratamiento antirretroviral, con diferentes estadios de progresión, 7 de los cuales son controladores (Carga viral <2000 copias/mL) y 16 progresores (Carga viral >2000 copias/mL), además de 7 controles sanos. En células mononucleares de sangre periférica, se cuantificaron los niveles de la expresión transcripcional de ABCA-1, ABCA-3, Caspasa-5 y TXNIP mediante RT-PCR. Se evaluó la asociación de estos parámetros con variables demográficas y de laboratorio, y se encontró que los individuos VIH-1 progresores mostraron niveles significativamente menores de TXNIP y ABCA-3, sugiriendo que durante la infección por VIH-1 se produce una alteración en la expresión de estas moléculas. Dada la complejidad de las interacciones inmuno-metabólicas durante la infección por VIH-1, se necesitan estudios adicionales para establecer los mecanismos precisos involucrados en estas alteraciones

Because antiretroviral therapy fails to control the immune activation that occurs during HIV-1 infection, the study of immunomodulatory molecules may provide alternative strategies for their control. In this sense, the aim of the research was to evaluate the transcriptional expression of molecules associated with the metabolism of high-density lipoproteins and with the inflammatory response mediated by the NLRP3 inflammasome in patients infected with HIV-1. This is a cross-sectional study, which included 23 HIV-1 patients without antiretroviral treatment, with different stages of progression, 7 of which are controllers (Viral load <2000 copies/mL) and 16 progressors (Viral load >2000 copies/mL), in addition to 7 healthy controls. In peripheral blood mononuclear cells, the levels of transcriptional expression of ABCA-1, ABCA-3, Caspase-5 and TXNIP were quantified by RT-PCR. The association of these parameters with laboratory and demographic variables was evaluated and it was found that HIV-1 progressing individuals showed significantly lower levels of TXNIP and ABCA-3, suggesting that during HIV-1 infection there is an alteration in the expression of these molecules. Given the complexity of the immuno-metabolic interactions during HIV-1 infection, additional studies are needed to establish the precise mechanisms involved in these alterations

[Evaluation of the usefulness of nail biopsy in the diagnosis of onychomycosis]. / Evaluación de la utilidad diagnóstica de la biopsia ungueal en las onicomicosis.

BACKGROUND: Onychomycosis affects between 2% to 30% of the world population. Nail biopsy may help in making a diagnosis and can distinguish between invasion and colonisation. AIMS: To evaluate the diagnostic usefulness of nail biopsy with Periodic acid-Schiff (PAS) staining for onychomycosis, compared to direct KOH examination, culture and its combination in a reference laboratory in Colombia. METHODS: The study included 66 patients in whom a blind and independent reading of the three tests was performed. The usefulness was defined based on the validity (sensitivity, specificity, Youden's index, likelihood ratios), performance (predictive values) efficiency (proportion of correctly diagnosed patients), and reproducibility (kappa coefficient). RESULTS: The mean age of the patients was 55±16 years, and included 76% women. The direct tests with KOH were positive in 66.7% (n=44), 62.1% (n=41) were positive with culture, and 56.1% (n=37) with the biopsy. The main causal agents were non-dermatophytes moulds in 36.4% (n=24). The most frequent species were Neoscytalidium dimidiatum (n=11), Trichophyton rubrum (n=11), and Candida parapsilosis (n=13). The sensitivity of nail biopsy, when compared to the standard (KOH and/or culture), was 71%, specificity 83%, Youden's index 0.54, positive likelihood ratio 4.25, negative likelihood ratio 0.35, positive predictive value 92%, negative predictive value 52%, efficiency 74% and kappa coefficient 0.45. When biopsy was evaluated only in patients with onycholysis of the nail plate greater than 50%, all the parameters of diagnostic usefulness increased. CONCLUSIONS: The overall usefulness of the biopsy was moderate for patients with more severe symptomatology, which makes its use advisable in cases of extensive onycholysis, and when discriminating colonisation from invasion is required.

Study of interaction energies between residues of the active site of Hsp90 and geldanamycin analogues using quantum mechanics/molecular mechanics methods.

Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used.  Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodology (Autodock-PM6) and DFT indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: This study contributes with new hybrid methodology (Autodock-PM6) for the generation of 3DQSAR models, which to consider the interactions between compounds and amino acids residues of Hsp90´s active site in the alignment generation. Additionally, quantum similarity and reactivity indices calculations using DFT were performed to know the non-covalent stabilization in the active site of these compounds.

Layered Approach to the Anterior Knee: Normal Anatomy and Disorders Associated with Anterior Knee Pain.

Anterior knee pain is a common complaint that can be caused by a wide spectrum of disorders affecting the many varied tissues at the anterior knee. The anatomy and pathologic conditions of the anterior knee can be approached systematically by organizing the region into four layers: (a) superficial layer of fat, fascia, and bursae; (b) functional layer composed of the extensor mechanism and patellar stabilizers; (c) intracapsular extrasynovial layer containing the fat pads; and (d) intra-articular layer. The superficial layer is composed of delicate tissues that are predisposed to blunt and penetrating trauma, irritation, and infection. The extensor mechanism forms the functional layer, is responsible for knee extension and patellar stabilization, and is engaged in repetitive movements; overuse disorders dominate in this layer. The fat pads of the anterior knee are discussed collectively as an extracapsular extrasynovial layer, functioning to improve congruence and protect the articular surfaces during motion. Diseases involving the fat pads can be primary or secondary to pathologic conditions in the rest of the joint. The synovial lining and cartilage surface are in the fourth and final intra-articular layer; pathologic conditions are centered around arthritides and internal derangement. Symptoms in the anterior knee may be due to conditions affecting one or more of these interrelated layers. ©RSNA, 2018.

Aspergilosis pulmonar invasora en pacientes pediátricos con trasplante hepático, a propósito de una sobreviviente / Invasive pulmonary aspergillosis in children with hepatic transplant: a survivor

INTRODUCCIÓN: Las infecciones por Aspergillus spp son la principal infección micótica por hongos en pacientes con trasplante hepático, con una mortalidad reportada de hasta un 90% de los casos. En los pacientes trasplantados de hígado se espera que hasta un 50% desarrollen un episodio infeccioso en sus primeros meses postrasplante, de los cuales un 10% se asocian con agentes oportunistas. OBJETIVO: Describir el diagnóstico y manejo de un episodio de Aspergilosis Pulmonar Invasora (API) en una paciente con un trasplante hepático CASO CLÍNICO: Paciente de 11 meses de vida, con trasplante hepático secundario a atresia de vías biliares. En el periodo post-trasplante inmediato evolucionó con una neumonía grave asociada a ventilación mecánica. El lavado broncoalveolar presentó niveles altos de galactomanano y cultivo positivo para Aspergillus fumigatus, diagnosticándose una API. Este episodio se trató con un esquema de antifúngico con un resultado clínico favorable. CONCLUSIÓN: La API es una infección oportunista en pacientes con trasplante hepático, que debe ser sospechada en este grupo de pacientes, ya que el diagnóstico y tratamiento oportuno impacta directamente en la resolución de la infección por Aspergillus fumigatus.

INTRODUCTION: Mycotic infections due to Aspergillus spp, are the main mycotic associated infections in liver transplant patients, with mortality rates up to 90% of the cases. Almost 50% of patients will de velop an infection during the first months after transplantation, of which 10% are associated with op portunistic agents. OBJECTIVE: To describe the diagnosis and management of an Invasive Pulmonary Aspergillosis (IPA) episode in a liver transplant patient. CASE-REPORT: 11-months-old patient with liver transplant due to a biliary atresia who developed severe pneumonia associated with mechanical ventilation. The bronchoalveolar lavage showed high levels of galactomannan and positive culture for Aspergillus fumigatus leading to an IPA diagnosis. This episode was treated with antifungal with a favorable outcome. CONCLUSION: The IPA is an opportunistic infection in liver transplant patients, with high mortality rates, that must be suspected in this group of patients since an early diagnosis and treatment reduce mortality.

MR Imaging of Atraumatic Muscle Disorders.

Atraumatic disorders of skeletal muscles include congenital variants; inherited myopathies; acquired inflammatory, infectious, or ischemic disorders; neoplastic diseases; and conditions leading to muscle atrophy. These have overlapping appearances at magnetic resonance (MR) imaging and are challenging for the radiologist to differentiate. The authors organize muscle disorders into four MR imaging patterns: (a) abnormal anatomy with normal signal intensity, (b) edema/inflammation, (c) mass, and (d) atrophy, highlighting each of their key clinical and imaging findings. Anatomic muscle variants, while common, do not produce signal intensity alterations and therefore are easily overlooked. Muscle edema is the most common pattern but is nonspecific, with a broad differential diagnosis. Autoimmune, paraneoplastic, and drug-induced myositis tend to be symmetric, whereas infection, radiation-induced injury, and myonecrosis are focal asymmetric processes. Architectural distortion in the setting of muscle edema suggests one of these latter processes. Intramuscular masses include primary neoplasms, metastases, and several benign masslike lesions that simulate malignancy. Some lesions, such as lipomas, low-flow vascular malformations, fibromatoses, and subacute hematomas, are distinctive, but many intramuscular masses ultimately require a biopsy for definitive diagnosis. Atrophy is the irreversible end result of any muscle disease of sufficient severity and is the dominant finding in disorders such as the muscular dystrophies, denervation myopathy, and sarcopenia. This imaging-based classification, in correlation with clinical and laboratory data, will aid the radiologist in interpreting MR imaging findings in patients with atraumatic muscle disorders. ©RSNA, 2018.

Seguimiento inmunológico con anticuerpos anti-HLA por tecnología Luminex™, ¿se puede prevenir el rechazo agudo celular y humoral en trasplante de intestino? / Anti-HLA antibody immunological follow up by the Luminex TM. Is it possible to prevent the acute cell and humoral immune rejection in small bowel transplant? Report of one case

Introducción. El trasplante de intestino mejora la supervivencia de pacientes con falla intestinal secundaria al síndrome de intestino corto. Estos receptores tienen gran riesgo de rechazo agudo, por lo cual, de manera protocolaria y como método de referencia, se practican biopsias intestinales. En este reporte de caso se hizo el seguimiento inmunológico de anticuerpos anti-HLA por tecnología Luminex™ (LSA) de un paciente con trasplante de intestino más biopsias por protocolo para un diagnóstico temprano, y una adecuada correlación histológica. Presentación del caso. Se trata de un paciente de 20 años de edad con síndrome de intestino corto, que ingresó a la Fundación Valle del Lili (Cali, Colombia) y requirió un trasplante aislado de intestino. El seguimiento inmunológico se hizo con tecnología Luminex™ y biopsias intestinales mensuales. Según la tamización contemplada en el protocolo previo al trasplante, el paciente tuvo anticuerpos anti-HLA (PRA de clase I y II) negativos; y a los 11 meses después del trasplante, los anticuerpos anti-HLA de clase I y II fueron positivos. Con la prueba de LSA se detectó un anticuerpo específico contra donantes (Donor Specific Antibodies, DSA) y varios anticuerpos contra otros subtipos moleculares. Se tomó una biopsia que mostró un leve rechazo celular agudo y se inició tratamiento con plasmaféresis. Hasta 21 meses después del trasplante, el paciente no ha presentado rechazos clínicos y ha tenido una adecuada evolución clínica y paraclínica Conclusión. Este es el primer trasplante de intestino en nuestro centro, en el que se hace seguimiento inmunológico con tecnología Luminex™. Consideramos que la detección con DSA es un buen marcador de rechazo agudo humoral, que permitiría una aproximación diagnóstica y una intervención oportuna

Background: Small bowel transplant improves survival of the recipients that have intestinal failure secondary to short bowel syndrome. These patients have a high risk of acute rejection; for this reason bowel biopsies are performed as protocol and is the gold standard. Immunological follow-up of anti-HLA antibodies with Luminex® technology (LSA) was carried out in a patient with intestinal transplant and biopsies were performed to achieve an early diagnosis and a suitable histological correlation. Case report: A 20-year-old patient with short bowel syndrome secondary to extensive intestinal resection due to a complicated appendicitis underwent isolated bowel transplantation. The post-transplant immunological follow-up was performed with LSA and monthly intestinal biopsies. Antibodies with mean fluorescence intensity greater than 1500 were positive. During the pre-transplant protocol, the patient was screened for anti-HLA antibodies with negative results. Eleven months post-transplant, the screening test for anti-HLA Class I and II antibodies was positive; the specificity of the LSA test detected one specific donor antibody (DSA) and several antibodies against other molecular subtypes. The biopsy result was a mild acute cellular rejection and plasmapheresis therapy was started. The patient has not presented a clinical rejection, and at 21 months post-transplantation exhibits an adequate clinical and paraclinical evolution. Conclusions: This is the first small bowel transplant where immunological follow-up is done with LSA. We believe that the detection of DSA is a marker of acute humoral rejection that allows a diagnostic approach and a timely intervention

Aporte de la biorremediación para solucionar problemas de contaminación y su relación con el desarrollo sostenible / Contribution of bioremediation to solve pollution problems and its relationship with sustainable development

Resumen Introducción: La biorremediación, se ha convertido en una alternativa atractiva y prometedora a las tradicionales técnicas físico-químicas para la remediación de los compuestos que contaminan el ambiente. Objetivo: Revisión sobre la aplicación de la biorremediación y su aporte en el al cumplimiento de uno de los objetivos de desarrollo sostenible. Materiales y métodos: Estudio descriptivo mediante la revisión documental sobre las posibilidades y limitaciones que presenta esta biotecnología en el tratamiento de problemas de contaminación. Resultados: Entre las principales tecnologías que se han registrado desde la década de 1970, la biorremediación ha demostrado ser rentable y eficiente en la remoción de determinados contaminantes. Conclusión: A pesar de los beneficios de las tecnologías de biorremediación, existen algunas dificultades en la aplicación debido a las restricciones impuestas por el sustrato y variabilidad ambiental, el potencial limitado de biodegradación y la viabilidad de los microorganismos de origen natural, entre otras.

Abstract Introduction: Bioremediation is an alternative to traditional physico-chemical techniques for the remediation of compounds that pollute the environment. Objective: To review the application of bioremediation and its contribution to the fulfillment of one of the objectives of sustainable development. Materials and methods: A descriptive study was made by means of documentary review about the possibilities and limitations of biotechnology in the treatment of problems of contamination. Results: Among the main technologies that have been registered since the decade of 1970, bioremediation has proven to be profitable and efficient in the removal of certain pollutants. Conclusions: Despite the benefits of bioremediation technologies, there are some difficulties in the application due to the restrictions imposed by the substrate and environmental variability, the limited potential of biodegradation and the viability of microorganisms of natural origin, among others.

Hepatoblastoma: Transplant Versus Resection Experience in a Latin American Transplant Center.

BACKGROUND: Hepatoblastoma is the most common primary malignant liver tumor in children and is usually diagnosed during the first 3 years of life. Overall survival has increased 50% due to chemotherapeutic schemes, expertise surgery centers, and liver transplantation. METHODS: A retrospective collection of data was performed from pediatric patients with diagnosis of hepatoblastoma. Variables included demographic, diagnostic tools and histological classification; chemotherapy and surgical treatment; and outcomes and patient survival. The PRETEXT classification was applied, which included the risk evaluation, and according to the medical criterion in an individualized way, underwent resection or transplant. The morbidity of patients was evaluated by the Clavien-Dindo classification. Statistical analysis was performed according to the distribution of data and the survival analysis was carried out using the Kaplan-Meier method. RESULTS: The patients (n = 16) were divided in a resection group (n = 8) and a transplant group (n = 8). The median age at the time of diagnosis was 13.5 months. The motive for the initial consultation was the discovery of a mass; all patients had high levels of α-fetoprotein and an imaging study. Ten of 16 patients required chemotherapy before the surgical procedure. In the resection group, 5 of 8 patients were classified as Clavien I and 4 of 8 patients of the transplant group were classified as Clavien II. Patient survival at 30 months was 100% in the resection group and 65% in the liver transplantation group. CONCLUSIONS: To our knowledge, this is the first case report of pediatric patients with hepatoblastoma and liver resection or transplant in Colombia and Latin America. Our results are comparable with the series worldwide, showing that resection and transplant increase the survival of the pediatric patients with hepatoblastoma. It is important to advocate for an increase of reporting in the scientific literature in Latin America.