Synthesis and toxicity of monothiooxalamides against human red blood cells, brine shrimp (Artemia salina), and fruit fly (Drosophila melanogaster).

A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by 1H and 13C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (I). In this study, the in vitro hemolytic activity of compounds from the 2-aminopyridine (I) and 2-aminobenzimidazole (II) families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and in vivo toxicity against Drosophila melanogaster. Compounds with morpholine fragments (1g, 1h, 2g, and 2h) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide 2g showed lower toxicity and can be considered for further biological screening and application trials.

SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022).

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.

Association of class II HLA alleles with susceptibility to develop immune-mediated diseases in Paraguayan patients.

Genetic and nongenetic factors are involved in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). The best-known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA-DRB1*03:01 and HLA-DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs.

Detección de mutaciones del Gen KRAS en pacientes paraguayos con cáncer colorrectal / Detection of KRAS Gene mutations in paraguayan patients with colorectal cancer

El estado mutacional del KRAS ha sido considerado como biomarcador para tratamientos biológicos tras varios ensayos clínicos realizados en pacientes con cáncer colorrectal metastásico. Reportes recientes indican que las frecuencias de mutación del gen KRAS en pacientes con CCR de Asia, Europa y Latinoamérica están entre el 24%, 36% y 40%, respectivamente. Paraguay no cuenta con este tipo de informes, a pesar de registrar anualmente en promedio 75 nuevos casos de pacientes diagnosticados con CCR sólo en el Servicio de Cirugía General del Hospital Central del Instituto de Previsión Social (IPS). El presente trabajo ha implementado este análisis de rutina, prerrequisito obligatorio para la administración de fármacos basados en anticuerpos terapéuticos, y revelado una frecuencia de mutación del gen KRAS del 34% en pacientes paraguayos con CCR que acuden a los Servicios del Hospital Central del IPS

The mutational status of the KRAS has been consider as a biomarker for biological treatments after several clinical trials carried out in patient with metastatic colorectal cancer. Recent reports indicate that the KRAS gene mutation frequencies in CRC patients from Asia, Europe, and Latin America are between 24%, 36%, and 40%, respectively. Paraguay does not have this kind of reports, despite registering an average of 75 new cases of patients diagnosed with CRC per year only in the General Surgery Service of the "Central Hospital - Instituto de Prevision Social (IPS)". The present work has implemented this routine analysis, a mandatory prerequisite for the administration of drugs based on therapeutic antibodies and revealed a KRAS gene mutation frequency of 34% in Paraguayan patients with CRC who attend the IPS Central Hospital Services

Relevance of codetection of respiratory viruses in the severity of acute respiratory infection in hospitalized children. / Relevancia de la co-detección de virus respiratorios en la severidad de la infección respiratoria aguda en niños hospitalizados.

INTRODUCTION: Multiplex polymerase chain reaction (PCR) allows simultaneous detection of respiratory viruses, raising questions about their relevance in the clinical feature. OBJECTIVE: To evaluate the contribution of clinical, epidemiological, and virological factors in the clinical course of children hospitalized due to ARI with viral co-detection. PATIENTS AND METHOD: Pediatric patients ≤ 15 years old, hospitalized due to ARI at the UC-CHRISTUS Health Network Clinical Hospital between June and October 2014, and who presented a positive respiratory molecular panel test, were included. Respiratory samples (nasopharyngeal swab, tracheal aspiration, or bronchoalveolar lavage) with positive panel tests by Seeplex® RV15 OneStep ACE Detection Seegene® technique, were analyzed with a second technique (xTAG-RVP-FASTv2 Luminex®, USA), which allows simultaneous and semi-quantitative detection of 17 respiratory viruses. Clinical and epidemiological records were collected. RESULTS: One virus was identified in 42/57 children (74%) and two or more in 15/57 (26%). Intensive care unit (ICU) hospi talization was significantly more frequent in patients with viral co-detection (OR = 5,5; IC 95%: 1,5 19,6). The most frequently detected viruses were rhinovirus/enterovirus (HRV/EV) (29%) and res piratory syncytial virus (RSV) (25%), and the most common co-detection was HRV/EV-RSV (33%). In x-rays, patients with HRV/EV infection presented interstitial images more frequently, while RSV was associated with condensations (p = 0.002). For HRV/EV, median fluorescence intensity (MFI, semi-quantification) were 1788 and 2456 in co-detection and single agent, respectively (p = 0.022). Children with HRV/EV co-detection had a longer hospital stay compared to isolated identification (5 versus 3 days, p = 0,028). CONCLUSION: In children hospitalized due to ARI, viral co-detection is frequent and associated with more ICU hospitalizations. Our study highlights the presence of HRV/ EV in viral co-detection and longer length of stay. More studies are needed to define the relevance of viral co-detection in hospitalized pediatric patients.

Plant Defensin γ-Thionin Induces MAPKs and Activates Histone Deacetylases in Bovine Mammary Epithelial Cells Infected With Staphylococcus aureus.

Defensins are an important group of host defense peptides. They have immunomodulatory properties, which have been mainly described for mammal defensins, but similar effects for plant defensins remain unknown. Previously, we showed that the defensin γ-thionin (Capsicum chinense) reduces Staphylococcus aureus internalization into bovine mammary epithelial cells (bMECs) while inducing Toll-like receptor 2 (TLR2), modulating the inflammatory response. Here, we analyze the effect of γ-thionin on the TLR2 pathway in bMECs infected with S. aureus and determine if it modulates epigenetic marks. Pre-treated bMECs with γ-thionin (100 ng/ml) reduced the basal activation of p38 and ERK1/2 (~3-fold), but JNK was increased (~1.5-fold). Also, infected bMECs induced p38, but this effect was reversed by γ-thionin, whereas ERK1/2 was reduced by infection but stimulated by γ-thionin. Likewise, γ-thionin reduced the activation of Akt kinase ~50%. Furthermore, γ-thionin induced the activation of transcriptional factors of inflammatory response, highlighting EGR, E2F-1, AP-1, and MEF, which were turned off by bacteria. Also, γ-thionin induced the activation of histone deacetylases (HDACs, ~4-fold) at 24 h in infected bMECs and reduced LSD1 demethylase (HDMs, ~30%) activity. Altogether, these results demonstrated the first time that a plant defensin interferes with inflammatory signaling pathways in mammalian cells.

Cromoforo fotoactivado con crosslinking como tratamiento para la queratitis por Acanthamoeba / Photoactivated chromophore with crosslinking as treatment for Acanthamoeba keratitis

RESUMEN Se reporta el uso del crosslinking como tratamiento de la queratitis por Acanthamoeba en una serie de 7 pacientes quienes acudieron al Servicio de Córnea por queratitis multitratadas. Se les realizó biopsia corneal, la cual se cultivó en solución de Page. Los pacientes fueron tratados con un protocolo de PACK-CXL durante más de 5 minutos y fueron sometidos a la exposición a la luz UV-A. El edema del nuevo epitelio era de 2 cruces a las 24 horas, y desapareció a las dos semanas del procedimiento en todos los casos. El porcentaje de desepitelización basal al momento del diagnóstico fue de 75,7 por ciento. La agudeza visual mejor corregida fue de entre 20/20 y 20/30. Se concluye que el uso de crosslinking en pacientes con Acanthamoeba en fases inicales pudiera ser una opción terapéutica segura y efectiva(AU)

ABSTRACT A report is presented of the use of crosslinking as treatment for Acanthamoeba keratitis in a series of 7 patients attending the Cornea Service for multitreated keratitis. Corneal biopsy was performed, which was cultured in Page solution. The patients were treated with a PACK-CXL protocol for more than 5 minutes and subjected to UV-A light exposure. Edema of the new epithelium was 2 crosses at 24 hours and disappeared 2 weeks after the procedure in all cases. Basal de-epithelialization percentage at diagnosis was 75.7 percent. Best corrected visual acuity ranged between 20/20 and 20/30. It is concluded that the use of crosslinking in patients with Acanthamoeba keratitis in its initial stages could be a safe and effective therapeutic option(AU)

Una Aplicación de una Historia Clínica Electrónica (HCE) Basado en Modelos Conceptuales para Integrar Datos Clínicos y Genómicos y Orientar la Estrategia Terapéutica

Actualmente, la gestión de datos en el departamento de oncología es compleja y requiere sistemas de información avanzados para procesar datos donde la información "ómica" debe integrarse junto con los datos clínicos del paciente para mejorar el análisis de datos y el proceso de toma de decisiones. Este trabajo de investigación presenta una experiencia práctica en este contexto. Se ha diseñado un Modelo Conceptual (MC) para desarrollar un Sistema de Información (SI) con el fin de gestionar datos clínicos, patológicos y moleculares de manera integral en el departamento de oncología de dos hospitales principales en Paraguay. Además, se han propuesto arquetipos basados en modelos para especificar la estrategia de interacción del usuario. El MC y los arquetipos asociados son la base para desarrollar un SI clínico con el fin de cargar -primero- y gestionar -segundo- todos los datos clínicos que requiere el dominio, mostrando cuán factible es el enfoque en la práctica y cuánto se mejora la gestión de datos. En este trabajo, queremos reforzar con esta experiencia real, cómo el uso correcto de un MC junto con los arquetipos ayuda a diseñar, desarrollar y administrar mejores sistemas de información, enfatizando la relevancia del dominio clínico seleccionado.

Currently, data management in oncology department is complex and requires advanced Information Systems (ISs) to process data where "omic" information should be integrated together with patient's clinical data to improve data analysis and decision-making process. This research paper reports a practical experience in this context. A Conceptual Model (CM) has been designed to develop an Information System (IS) in order to manage clinical, pathological, and molecular data in a holistic way at the oncology department of two main Hospitals in Paraguay. Additionally, model-based archetypes have been proposed to specify the selected user interaction strategy. The CM and its associated archetypes are the basis to develop a clinical IS in order to load -firstly- and manage -secondly- all the clinical data that the domain requires, showing how feasible the approach is in practice, and how much the corresponding clinical data management is improved. In this work, we want to reinforce with this real experience how using a CM along with archetypes correctly helps to design, develop and manage better information systems, emphasizing the relevance of the selected clinical domain.

An application of an EHR based on conceptual modeling to integrate clinical and genomic data and guide therapeutic strategy / Una aplicación de una Historia Clínica Electrónica (HCE) basado en modelos conceptuales para integrar datos clínicos y genómicos y orientar la estrategia

Actualmente, la gestión de datos en el departamento de oncología es compleja y requiere sistemas de información avanzados para procesar datos donde la información "ómica" debe integrarse junto con los datos clínicos del paciente para mejorar el análisis de datos y el proceso de toma de decisiones. Este trabajo de investigación presenta una experiencia práctica en este contexto. Se ha diseñado un Modelo Conceptual (MC) para desarrollar un Sistema de Información (SI) con el fin de gestionar datos clínicos, patológicos y moleculares de manera integral en el departamento de oncología de dos hospitales principales en Paraguay. Además, se han propuesto arquetipos basados en modelos para especificar la estrategia de interacción del usuario. El MC y los arquetipos asociados son la base para desarrollar un SI clínico con el fin de cargar -primero- y gestionar -segundo- todos los datos clínicos que requiere el dominio, mostrando cuán factible es el enfoque en la práctica y cuánto se mejora la gestión de datos. En este trabajo, queremos reforzar con esta experiencia real, cómo el uso correcto de un MC junto con los arquetipos ayuda a diseñar, desarrollar y administrar mejores sistemas de información, enfatizando la relevancia del dominio clínico seleccionado.

Currently, data management in oncology department is complex and requires advanced Information Systems (ISs) to process data where "omic" information should be integrated together with patient's clinical data to improve data analysis and decision-making process. This research paper reports a practical experience in this context. A Conceptual Model (CM) has been designed to develop an Information System (IS) in order to manage clinical, pathological, and molecular data in a holistic way at the oncology department of two main Hospitals in Paraguay. Additionally, model-based archetypes have been proposed to specify the selected user interaction strategy. The CM and its associated archetypes are the basis to develop a clinical IS in order to load -firstly- and manage -secondly- all the clinical data that the domain requires, showing how feasible the approach is in practice, and how much the corresponding clinical data management is improved. In this work, we want to reinforce with this real experience how using a CM along with archetypes correctly helps to design, develop and manage better information systems, emphasizing the relevance of the selected clinical domain

Prevalencia de valores inadecuados de vitamina D y factores de riesgo asociados en jóvenes universitarios de Asunción / Prevalence of inadequate vitamin D values and associated risk factors in university students of the city of Asunción

La vitamina D es una hormona cumple una función en la regulación de numerosos genes que participan en la proliferación y maduración celular. El objetivo de este trabajo fue determinar la prevalencia de valores inadecuados de esta vitamina en jóvenes sanos de Asunción e identificar los posibles factores de riesgo asociados. Estudio observacional descriptivo basado en datos clínico-epidemiológicos y en la determinación de la 25-hidroxivitamina D (25-OH vitamina D) por el método de quimioluminiscencia (CMIA). Se consideró valor adecuado ≥30 ng/dl, inadecuado por debajo de este rango y deficiente ≤20 ng/dl. El análisis estadístico se realizó con el programa R-proyect. Para establecer factores de riesgo para tener deficiencia de vitamina D se utilizó regresión logística bi y multivariante. Se incluyeron 817 jóvenes universitarios de edad promedio 21 años. La concentración de vitamina D tuvo una media de 25 ± 8 ng/dl, oscilando entre 64,3 y 2,4 ng/dl. El 75,5% de los participantes tenían valores inadecuados de vitamina D. La deficiencia de vitamina D fue significativamente (p = 0,006) más frecuente en mujeres, personas con sobrepeso (p = 0,03), con falta de exposición al sol (p = 0,001) y con sedentarismo (p = 0,0001). Este estudio confirma la elevada prevalencia de valores inadecuados de vitamina D en nuestro país y permite definir un perfil de muy alto riesgo para las jóvenes sedentarias y con sobrepeso, lo que justifica una atención especial de parte de los médicos y las instituciones responsables de la salud pública en nuestro país(AU)

Vitamin D is a hormone that plays a role in the regulation of numerous genes involved in cell proliferation and maturation. The objective of this work was to determine the prevalence of inadequate values of this vitamin in healthy young people of the city of Asunción and to identify the possible risk factors associated with it. Descriptive observational study based on clinical-epidemiological data and in the determination of 25-hydroxyvitamin D (25-OH vitamin D) by the chemiluminescence method (CMIA). It was considered appropriate values ≥30 ng/dl, inappropriate below this range and deficient <20 ng/dl. Statistical analyzes were carried out with the R-project program. To establish the association, bivariate and multivariate logistic regression was used. We included 817 university students with an average age of 21 years. The average value of the vitamin D concentration was 25 ± 8 ng/dl, ranging from 64.3 to 2.4 ng/dl. Inadequate vitamin D values were found in 75.5% of the participants. Vitamin D deficiency was significantly (p <0.006) more frequent in women, overweight people (p <0.03), lack of sun exposure (p = 0.001) and sedentary lifestyle (p = 0.0001). This study confirms the high prevalence of inadequate vitamin D values in our country and allows us to define a very high risk profile for sedentary and overweight young women, which justifies special attention from physicians and institutions responsible for public health in our country(AU)

Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy.

Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty-six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, Oncocarta Panel V.1 was applied to analyze the mutational profile from formalin-fixed paraffin-embedded samples. The microsatellite status was tested by immunohistochemistry (IHC). The mean age of the patients was 52 years with a range from 20 to 74 years. Eighty-three percent of the patients included in the study have advanced-stage tumors at the moment of the diagnosis. Sixteen patients (44.4%) were wild-type for all the oncogene regions analyzed with the Oncocarta panel. Thirty-two hot-spot pathogenic variants on seven oncogenes, among 20 patients (55.6%), were identified, including KRAS, NRAS, BRAF, PI3KCA, FGFR, epidermal growth factor receptor, and PDGFRA. Moreover, 14 (38.8%) of these patients presented pathogenic variants in KRAS/NRAS or BRAF genes that have implications in the clinical practice decisions. Five patients (14%) presented MSI. The IHC study for microsatellite status and the molecular profile analysis through Sequenom mass spectrometry are feasible and useful methods, due to identify those patient candidates for targeted therapies and for the budgetary calculations of the National Health Plans.

Transfixion technique for the treatment of silicone oil pupillary block glaucoma refractory to Nd-YAG iridotomy.

BACKGROUND: Pupillary block induced by silicon oil in vitrectomized patients is a common condition usually treated with Nd-YAG laser iridotomy or with surgical removal of silicon oil. CASE REPORT: A case of silicone oil pupillary block glaucoma successfully treated with a 30 G needle transfixion technique is described. We performed a non-complicated vitrectomy surgery for retinal detachment with proliferative vitreoretinopathy that included lensectomy, inferior peripheral iridectomy, and silicone oil injection. After surgery, the iridectomy became occluded with fibrous tissue and the intraocular pressure raised to 50 mmHg. After an initial Nd-YAG iridotomy was unsuccessful, we passed a 30 Ga needle through the sclerocorneal limbus and cut the fibrous tissue that blocked the iridectomy. This procedure restored the aqueous humor flow through the iridectomy, pushed back the silicone oil bubble into the vitreous cavity and lowered the intraocular pressure to normal levels. CONCLUSIONS: 30 Ga needle transfixion technique could be an effective, low cost, simple alternative for the treatment of silicone oil pupillary block in aphakic patients.

ANTECEDENTES: El bloqueo pupilar secundario a aceite de silicón en pacientes vitrectomizados es una condición frecuente que normalmente se trata con apertura de la iridectomía con láser Nd-YAG o con el retiro del aceite de silicón. CASO CLÍNICO: Se describe un caso de glaucoma secundario a bloqueo pupilar por aceite de silicón tratado satisfactoriamente con técnica de transfixión con aguja de calibre 30. Realizamos una cirugía de vitrectomía sin complicaciones para el tratamiento de un desprendimiento de retina con vitreorretinopatía proliferativa, que incluyó lensectomía, iridectomía periférica inferior e inyección de aceite de silicón. Después de la cirugía, la iridectomía se ocluyó con tejido fibroso y la presión intraocular se incrementó a 50 mmHg. Después de que una iridotomía inicial con láser Nd-YAG no tuvo éxito, pasamos una aguja de calibre 30 a través del limbo esclerocorneal y cortamos el tejido fibroso que bloqueaba la iridectomía. Este procedimiento restauró el flujo de humor acuoso a través de la iridectomía, desplazando la burbuja de aceite de silicón a la cavidad vítrea, y la presión intraocular descendió a valores normales. CONCLUSIONES: La técnica de transfixión con aguja de calibre 30 puede ser una alternativa efectiva, simple y de bajo costo para el tratamiento del bloqueo pupilar con aceite de silicón en pacientes con afaquia.

[Risk of recurrence in differentiated thyroid cancer]. / Riesgo de recurrencia en cáncer diferenciado de tiroides: escala MINSAL.

BACKGROUND: Differentiated thyroid cancer (DTC) is generally associated with a favorable prognosis. Its treatment requires surgery, selective use of radioiodine and levothyroxine, and its intensity must be adjusted to the initial risks of mortality and recurrence. AIM: To validate the risk of recurrence classification developed by the Chilean Ministry of Health in 2013 (MINSAL 2013), and compare it with the American Thyroid Association (ATA) 2009 and 2015 classifications. MATERIAL AND METHODS: Retrospective study of 362 patients with DTC aged 44.3 ± 13.4 years (84% women), treated with total thyroidectomy, selective radioiodine ablation and levothyroxine and followed for a median of 4.2 years (range 2.0-7.8). Risk of recurrence was estimated with MINSAL 2013, ATA 2009 and ATA 2015 classifications, and risk of mortality with 7th and 8th American Joint Committee on Cancer (AJCC)/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. RESULTS: A mean dose of 104 ± 48 mCi radioiodine was received by 91% of patients. MINSAL 2013 classified 148 (41%), 144 (40%), 67 (19%) and 3 (1%) patients as very low, low, intermediate and high risk of recurrence, respectively. Forty-five (12.4%) patients had persistence or recurrence during follow-up: 33 structural and 12 biochemical. Rates of persistence/recurrence on each category of MINSAL 2013 were 4.1%, 7.6%, 37.3% and 100%, respectively (p < 0.01). Areas under Receiver Operating Characteristic curves for persistence or recurrence of MINSAL 2013, ATA 2009 and ATA 2015 were 0.77 vs 0.73 vs 0.72, respectively. CONCLUSIONS: MINSAL 2013 classifies appropriately DTC patients and estimates correctly their risk of persistence or recurrence.

Riesgo de recurrencia en cáncer diferenciado de tiroides: escala MINSAL / Risk of recurrence in differentiated thyroid cancer

Background: Differentiated thyroid cancer (DTC) is generally associated with a favorable prognosis. Its treatment requires surgery, selective use of radioiodine and levothyroxine, and its intensity must be adjusted to the initial risks of mortality and recurrence. Aim: To validate the risk of recurrence classification developed by the Chilean Ministry of Health in 2013 (MINSAL 2013), and compare it with the American Thyroid Association (ATA) 2009 and 2015 classifications. Material and Methods: Retrospective study of 362 patients with DTC aged 44.3 ± 13.4 years (84% women), treated with total thyroidectomy, selective radioiodine ablation and levothyroxine and followed for a median of 4.2 years (range 2.0-7.8). Risk of recurrence was estimated with MINSAL 2013, ATA 2009 and ATA 2015 classifications, and risk of mortality with 7th and 8th American Joint Committee on Cancer (AJCC)/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results: A mean dose of 104 ± 48 mCi radioiodine was received by 91% of patients. MINSAL 2013 classified 148 (41%), 144 (40%), 67 (19%) and 3 (1%) patients as very low, low, intermediate and high risk of recurrence, respectively. Forty-five (12.4%) patients had persistence or recurrence during follow-up: 33 structural and 12 biochemical. Rates of persistence/recurrence on each category of MINSAL 2013 were 4.1%, 7.6%, 37.3% and 100%, respectively (p < 0.01). Areas under Receiver Operating Characteristic curves for persistence or recurrence of MINSAL 2013, ATA 2009 and ATA 2015 were 0.77 vs 0.73 vs 0.72, respectively. Conclusions: MINSAL 2013 classifies appropriately DTC patients and estimates correctly their risk of persistence or recurrence.

Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS•+. On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED50) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen.

Eventos cardiovasculares en pacientes con lupus eritematoso sistémico y su asociación con factores de riesgo cardiovascular / Cardiovascular events in patients with systemic lupus erythematosus and their association with cardiovascular risk factors

Los pacientes con lupus eritematoso sistémico (LES) presentan un elevado riesgo cardiovascular, cuya etiología aún no se conoce con exactitud. Se ha postulado que podrían estar implicados tanto los factores de riesgo cardiovascular tradicionales como determinados factores relacionados a la propia enfermedad. En el presente estudio, se ha analizado a un grupo de pacientes con LES y se ha determinado la presencia de eventos cardiovasculares (EC), así como también a los factores de riesgo cardiovascular (FRCV) tradicionales y los relacionados a la enfermedad. Además, se ha estudiado la asociación de estos últimos con el desarrollo de un EC (i.e. infarto de miocardio agudo, hipertensión arterial, accidente cerebrovascular). En el total de 83 pacientes analizados, el EC más frecuente fue la hipertensión arterial (HTA) en un 41%. En relación a los FRCV tradicionales, el sedentarismo fue el hallado con más frecuencia, seguido por la obesidad. Al analizar cada EC y su asociación con los FRCV, se observó una asociación significativa entre la HTA y la dislipidemia (p = 0,001). En relación a los accidentes cerebrovasculares, se observó una asociación con la edad avanzada (p = 0,037) y la presencia de síndrome antifosfolípido (p = 0,001). La elevada frecuencia de EC en los pacientes con diagnóstico de LES pone de manifiesto la necesidad de una evaluación inicial detallada para estratificar tanto FRCV tradicionales como los no tradicionales de los pacientes con LES para permitir una mejor supervisión y así mejorar el pronóstico cardiovascular de estos pacientes

Patients with systemic lupus erythematosus (SLE) have a high cardiovascular risk, whose etiology is not yet known accurately. It has been postulated that both traditional cardiovascular risk factors and certain factors related to the disease itself could be involved. In this study, we analyzed a group of patients with SLE and determined the presence of cardiovascular events (CE), and cardiovascular risk factors (CVRF), both traditional ones and those inherent to the disease. Besides, the association of the risk factors with the development of a CE (i.e. acute myocardial infarction, arterial hypertension (AHT), cerebrovascular accident) was studied. In a total of 83 patients, the most frequent CE was AHT in 41% of the patients. In relation to traditional CVRF, sedentary lifestyle was the most frequent (72%) followed by obesity. When we analyzed each CE and their association with the CVRF, we found a significant association between AHT and dyslipidemia (p = 0.001). In relation to cerebrovascular accidents, we observed an association with advanced age (p = 0.037) and presence of antiphospholipid syndrome (p = 0.001). The high frequency of CE in patients with diagnosis of SLE showed the need of a detailed initial assessment to stratify both traditional and non-traditional CVRF of a patient with SLE to allow a better monitoring and thus improve cardiovascular prognosis of these patients.

[Neurodevelopment in patients with retinopathy of prematurity treated with intravitreal bevacizumab. Case series]. / Neurodesarrollo en pacientes con retinopatía del prematuro tratados con bevacizumab intravítreo. Serie de casos.

BACKGROUND: Retinopathy of prematurity (ROP) is an eye disease caused by an alteration in retinal vasculogenesis that may lead to partial or complete vision loss with a harmful impact in terms of neurodevelopment. The purpose of the present study was to determine the neurodevelopment in patients with type i retinopathy of prematurity treated with intravitreal bevacizumab. MATERIAL AND METHODS: Case series. The inclusion criteria were: patients with type I ROP treated with a dose of 0.625mg/0.025ml of intravitreal bevacizumab. Demographic data and comorbidities were documented. Neurodevelopment was evaluated with the screening test of the Bayley Scale of Infant Development (BSID) in all patients between 11 and 28 weeks of age. RESULTS: Seven patients were included in the study. Four patients showed normal neurodevelopment according to the overall scores of the BSID scale. The distribution of high risk for neurodevelopmental delay in the different areas evaluated were as follows: 3 patients presented it in the cognitive area, one in the receptive communication area, one in the expressive area, one in the fine motor skills and 3 patients in the gross motor skills area. CONCLUSIONS: In these case series, the majority of patients treated with intravitreal bevacizumab for ROP showed normal neurodevelopment scores.

Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage.

Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.