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The development of antiprogestins was initially a gynecological purpose. However, since mifepristone was developed, its application for breast cancer treatment was immediately proposed. Later, new compounds with lower antiglucocorticoid and antiandrogenic effects were developed to be applied to different pathologies, including breast cancer. We describe herein the studies performed in the breast cancer field with special focus on those reported in recent years, ranging from preclinical biological models to those carried out in patients. We highlight the potential use of antiprogestins in breast cancer prevention in women with BRCA1 mutations, and their use for breast cancer treatment, emphasizing the need to elucidate which patients will respond. In this sense, the PR isoform ratio has emerged as a possible tool to predict antiprogestin responsiveness. The effects of combined treatments of antiprogestins together with other drugs currently used in the clinic, such as tamoxifen, CDK4/CDK6 inhibitors or pembrolizumab in preclinical models is discussed since it is in this scenario that antiprogestins will be probably introduced. Finally, we explain how transcriptomic or proteomic studies, that were carried out in different luminal breast cancer models and in breast cancer samples that responded or were predicted to respond to the antiprogestin therapy, show a decrease in proliferative pathways. Deregulated pathways intrinsic of each model are discussed, as well as how these analyses may contribute to a better understanding of the mechanisms involved.

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Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography-tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.

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OBJECTIVE.: To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. MATERIALS AND METHODS.: We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. RESULTS.: We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. CONCLUSIONS.: We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.

OBJETIVOS.: Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta¼ en el tratamiento de pacientes hospitalizados por la COVID-19. MATERIALES Y MÉTODOS.: Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. RESULTADOS.: Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. CONCLUSIONES.: Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

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Objetivos. Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta» en el tratamiento de pacientes hospitalizados por la COVID-19. Materiales y métodos. Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. Resultados. Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. Conclusiones. Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

Objective. To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. Materials and Methods. We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. Results. We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. Conclusions. We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.

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Introducción: La pandemia por el SARS-CoV-2 estableció desafíos para los sistemas de salud en función de dar continuidad a la atención de los pacientes por medio de la rápida adopción de la telesalud. Esto conllevó retos para los profesionales que se enfrentaron a las tecnologías de la información y la comunicación. Objetivos: Identificar conocimientos, habilidades, actitudes y prácticas de los profesionales de la salud que emplearon la telesalud en el ámbito ambulatorio durante la pandemia y analizar los posibles factores relacionados con las barreras que presentan los profesionales para implementar de forma efectiva los servicios de telesalud. Métodos: Estudio descriptivo de corte transversal analítico. Se aplicó una encuesta electrónica a profesionales de salud de tres centros médicos de Colombia. Resultados: Se aplicaron 430 encuestas. La mediana de edad fue de 39 años y el 79 % fueron mujeres. El 57 % no habían sido capacitados en aspectos técnicos, normativos y éticos de la telesalud; el 46 % reportó dificultad para administrar el tiempo; el 81 % manifestó el aumento en su carga laboral. La dificultad para emplear las herramientas tecnológicas se asoció 4,67 veces más a la percepción de alteración de su propio estado de salud; sin embargo, el 92 % manifestó que seguiría usando la telesalud. Conclusiones: La actitud frente al uso de la telesalud fue positiva; el conocimiento, habilidades y entrenamiento en telesalud parece determinar su aceptabilidad. Esta es una primera evaluación que revela los puntos a trabajar en el caso de los profesionales, en función de la permanencia de la telesalud como herramienta para la atención de pacientes.

Introduction: The SARS-CoV-2 pandemic posed challenges for health systems in terms of providing continuity of patient care through the rapid adoption of telehealth. This brought challenges for professionals who dealt with information and communication technologies. Objectives: To identify knowledge, skills, attitudes, and practices of health professionals who used telehealth in the outpatient setting during the pandemic and to analyze possible factors related to the barriers that professionals present to effectively implement telehealth services. Methods: This is a descriptive analytical cross-sectional study. An electronic survey was used on health professionals from three medical centers in Colombia. Results: Four hundred thirty (430) surveys were used. The median age was 39 years and 79% were women. 57% had not been trained in technical, regulatory and ethical aspects of telehealth; 46% reported difficulty managing time; 81% reported an increase in their workload. The difficulty in using technological tools was associated 4.67 times more with the perception of alteration of their own state of health; however, 92% said they would continue to use telehealth. Conclusions: The attitude towards the use of telehealth was positive; knowledge, skills, and training in telehealth seem to determine its acceptability. This is a first evaluation that reveals the points to work on in the case of professionals, based on the permanence of telehealth as a tool for patient care.

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The study aimed to evaluate a group of health professionals' knowledge, attitudes, and practices on pharmacovigilance in the context of COVID-19 in the Peruvian Social Health Insurance (EsSalud). A descriptive secondary analysis was carried out on a database that included responses from an online survey conducted by the Institutional Referral Center for Pharmacovigilance and Technovigilance of EsSalud. Of 144 participants, 66% showed a high level of knowledge and 81.2% had a positive attitude; however, 71.5% had an inadequate level of pharmacovigilance practice. Although EsSalud professionals demonstrated a high level of knowledge and positive attitude to implement pharmacovigilance, this is not reflected in the practice of this activity during the SARS-CoV-2 pandemic. Strategies should be implemented to integrate pharmacovigilance into healthcare activities to benefit patient safety.

El estudio tuvo como objetivo evaluar el conocimiento, las actitudes y prácticas de un grupo de profesionales de la salud sobre la farmacovigilancia en el contexto de la COVID-19 en el Seguro Social de Salud del Perú (EsSalud). Se realizó un análisis secundario descriptivo de una base de datos que incluía las respuestas de una encuesta en línea realizada por el Centro de Referencia Institucional de Farmacovigilancia y Tecnovigilancia de EsSalud. De 144 participantes, el 66% mostró alto nivel de conocimiento y el 81,2%, actitud positiva; sin embargo, el 71,5% tuvo un inadecuado nivel de práctica de farmacovigilancia. Si bien los profesionales de EsSalud demostraron tener alto conocimiento y actitud positiva para implementar farmacovigilancia, esto no se ve reflejado en la práctica de esta actividad en la época de pandemia por el SARS-CoV-2. Se deben emplear estrategias para integrar a la farmacovigilancia en las actividades asistenciales en beneficio de la seguridad del paciente.

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RESUMEN El estudio tuvo como objetivo evaluar el conocimiento, las actitudes y prácticas de un grupo de profesionales de la salud sobre la farmacovigilancia en el contexto de la COVID-19 en el Seguro Social de Salud del Perú (EsSalud). Se realizó un análisis secundario descriptivo de una base de datos que incluía las respuestas de una encuesta en línea realizada por el Centro de Referencia Institucional de Farmacovigilancia y Tecnovigilancia de EsSalud. De 144 participantes, el 66% mostró alto nivel de conocimiento y el 81,2%, actitud positiva; sin embargo, el 71,5% tuvo un inadecuado nivel de práctica de farmacovigilancia. Si bien los profesionales de EsSalud demostraron tener alto conocimiento y actitud positiva para implementar farmacovigilancia, esto no se ve reflejado en la práctica de esta actividad en la época de pandemia por el SARS-CoV-2. Se deben emplear estrategias para integrar a la farmacovigilancia en las actividades asistenciales en beneficio de la seguridad del paciente.

ABSTRACT The study aimed to evaluate a group of health professionals' knowledge, attitudes, and practices on pharmacovigilance in the context of COVID-19 in the Peruvian Social Health Insurance (EsSalud). A descriptive secondary analysis was carried out on a database that included responses from an online survey conducted by the Institutional Referral Center for Pharmacovigilance and Technovigilance of EsSalud. Of 144 participants, 66% showed a high level of knowledge and 81.2% had a positive attitude; however, 71.5% had an inadequate level of pharmacovigilance practice. Although EsSalud professionals demonstrated a high level of knowledge and positive attitude to implement pharmacovigilance, this is not reflected in the practice of this activity during the SARS-CoV-2 pandemic. Strategies should be implemented to integrate pharmacovigilance into healthcare activities to benefit patient safety.

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Galectin-1 (GAL1), a ß-galactoside-binding protein abundantly expressed in the tumor microenvironment, has emerged as a key mechanism of chemoresistance developed by different tumors. Although increased expression of GAL1 is a hallmark of hepatocellular carcinoma (HCC) progression, aggressiveness and metastasis, limited information is available on the role of this endogenous lectin in HCC resistance to chemotherapy. Moreover, the precise mechanisms underlying this effect are uncertain. HCC has evolved different mechanisms of resistance to chemotherapy including those involving the P-glycoprotein (P-gp), an ATP-dependent drug efflux pump, which controls intracellular drug concentration. Here, we investigated the molecular mechanism underlying GAL1-mediated chemoresistance in HCC cells, particularly the involvement of P-gp in this effect. Our results show that GAL1 protected HepG2 cells from doxorubicin (DOX)- and sorafenib-induced cell death in vitro. Accordingly, GAL1-overexpressing HepG2 cells generated DOX-resistant tumors in vivo. High expression of GAL1 in HepG2 cells reduced intracellular accumulation of DOX likely by increasing P-gp protein expression rather than altering its membrane localization. GAL1-mediated increase of P-gp expression involved activation of the phosphatidylinositol-3 kinase (PI3K) signaling pathway. Moreover, 'loss-of-function' experiments revealed that P-gp mediates GAL1-driven resistance to DOX, but not to sorafenib, in HepG2 cells. Conversely, in PLC/PRF/5 cells, P-gp protein expression was undetectable and GAL1 did not control resistance to DOX or sorafenib, supporting the critical role of P-gp in mediating GAL1 effects. Collectively, our findings suggest that GAL1 confers chemoresistance in HCC through mechanisms involving modulation of P-gp, thus emphasizing the role of this lectin as a potential therapeutic target in HCC.

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Progesterone receptors (PRs) ligands are being tested in luminal breast cancer. There are mainly two PR isoforms, PRA and PRB, and their ratio (PRA/PRB) may be predictive of antiprogestin response. Our aim was to investigate: the impact of the PR isoform ratio on metastatic behaviour, the PR isoform ratio in paired primary tumours and lymph node metastases (LNM) and, the effect of antiprogestin/progestins on metastatic growth. Using murine and human metastatic models, we demonstrated that tumours with PRB > PRA (PRB-H) have a higher proliferation index but less metastatic ability than those with PRA > PRB (PRA-H). Antiprogestins and progestins inhibited metastatic burden in PRA-H and PRB-H models, respectively. In breast cancer samples, LNM retained the same PRA/PRB ratio as their matched primary tumours. Moreover, PRA-H LNM expressed higher total PR levels than the primary tumours. The expression of NDRG1, a metastasis suppressor protein, was higher in PRB-H compared to PRA-H tumours and was inversely regulated by antiprogestins/progestins. The binding of the corepressor SMRT at the progesterone responsive elements of the NDRG1 regulatory sequences, together with PRA, impeded its expression in PRA-H cells. Antiprogestins modulate the interplay between SMRT and AIB1 recruitment in PRA-H or PRB-H contexts regulating NDRG1 expression and thus, metastasis. In conclusion, we provide a mechanistic interpretation to explain the differential role of PR isoforms in metastatic growth and highlight the therapeutic benefit of using antiprogestins in PRA-H tumours. The therapeutic effect of progestins in PRB-H tumours is suggested.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, representative samples from circulating SARS-CoV-2 in Colombia between January and April 2021, were processed for genome sequencing and lineage determination following the nanopore amplicon ARTIC network protocol and PANGOLIN pipeline. This strategy allowed us to identify the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several substitutions affecting the Spike protein, including the amino acid changes I95I, Y144T, Y145S and the insertion 146 N in the N-terminal domain, R346K, E484K and N501Y in the Receptor binding Domain (RBD) and P681H in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlantico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.

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OBJECTIVE: Assess the prevalence and types of digital technology use, as well as the extent to which patients use the internet and mobile devises. Evaluate the socioeconomic characteristics of patients and the possible relation to patterns of technology use in Colombia. Understand the nature of patient technology use in primary care for finding medical information. METHODS: A survey was applied to adult patients who attended primary health care centers systems in 6 Colombian cities. The survey inquired about demographic characteristics, insurance, access to services, cell phone use, internet access, and the use of such technology to access health-related services and information. Data was collected and managed using REDCap. Summary statistics on each survey item were calculated and the differences between discrete variables were analyzed using chi-square. Multivariate analyses were performed using logistic regression analysis for binary dependent variables. RESULTS: A total of 1580 patients were surveyed across the six study sites. 93% of the patients reported they have a cell phone. Patients from urban healthcare centers showed a higher use of the Internet on their phone than less urban settings. Around half of the surveyed patients reported Internet use (49.7%). Among Internet users, 65% of participants use the Internet looking for health care information. Around one-third of patients use cellphones to arrange clinic visits. Around 24% of participants answered positively for both Whooley's questions. Of those who screened positive on the Whooley questions, 43% reported being moderately anxious, 47% reported being very anxious. 51% reported having moderate pain; 52% reported having severe pain. CONCLUSIONS: The patterns of technology use identified in this study are essential for developing future health interventions based on ICT. The design of ICT clinical interventions must take into account the cellphone payment plans, availability of internet connection, advantages, and disadvantages of messenger services, including SMS as a possible alternative to people who do not have smartphones.

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Objetivo:Determinar los factores de riesgo de infección para Pseudomonas aeruginosa multirresistente en pacientes con Neumonía asociada a ventilación de la unidad de cuidados intensivos.:Serealizóunestudioobservacional,analítico, MaterialyMétodosretrospectivo, de casos y controles en el cual se seleccionaron mediante aleatorización simple 84 historias clínicas de pacientes con edad ≥ 18 años, con diagnóstico de neumonía asociada a ventilación mecánica en el Hospital Alta Complejidad Virgen de la Puerta (HACVP) y Hospital Belén de Trujillo (HBT) durante el periodo de enero-2014 a diciembre-2019. En el análisis de datos se utilizó la prueba Chi-cuadrado para determinar la significancia estadística de asociación en las variables de estudio. :La edad, uso de antibioticoterapia previa Resultadosde amplio espectro, uso de sonda vesical, tiempo de uso de sonda vesical y postoperado de cirugía abdominal, se asociaron significativamente (P<0,05) a infección por Pseudomonas aeruginosa multirresistente en pacientes con neumonía asociada a ventilación mecánica de la unidad de cuidados intensivos. El tiempo de exposición de sonda vesical es factor de riesgo para infección por Pseudomonas aeruginosa multirresistente (p<0.001). : El Conclusionestiempo de uso de sonda vesical por más de 7 días sin recambio de sonda es un factor de riesgo para infección por Pseudomonas aeruginosa multirresistente en pacientes con neumonía asociada a ventilación mecánica.

Objective:Determine the risk factors for multidrug-resistant Pseudomonas aeruginosa infection in patients with pneumonia associated with mechanical ventilation in the intensive care unit. :An observational, analytical, retrospective, case-control Material and Methodsstudy was carried out in which 84 medical records of patients aged ≥ 18 years with a diagnosis of ventilator-associatedpneumoniawereselectedbysimplerandomizationattheAlta Complejidad Hospital Virgen de la Puerta (HACVP) and Hospital Belén de Trujillo (HBT) during the period from January-2014 to December-2019. In the data analysis, the Chi-square test was used to determine the statistical significance of association in the study variables. :ResultsAge, use of prior broad-spectrum antibiotic therapy, use of urinary catheter, time of urinary catheter use, and postoperative abdominal surgery were significantly associated (P<0,05) with multidrug-resistant Pseudomonas aeruginosa infection in patients with pneumonia associated with intensive care unit mechanical ventilation. Urinary catheter exposure time is a risk factor for multidrug-resistant Pseudomonas aeruginosa infection (p <0.001). :The time Conclusionsof use of the urinary catheter for more than 7 days without change the catheter is a risk factor for infection by multidrug-resistant Pseudomonas aeruginosa in patients with pneumonia associated with mechanical ventilation.

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RESUMEN Objetivo: Determinar los factores de riesgo de infección para Pseudomonas aeruginosa multirresistente en pacientes con Neumonía asociada a ventilación de la unidad de cuidados intensivos. Material y Métodos: Se realizó un estudio observacional, analítico, retrospectivo, de casos y controles en el cual se seleccionaron mediante aleatorización simple 84 historias clínicas de pacientes con edad ≥ 18 años, con diagnóstico de neumonía asociada a ventilación mecánica en el Hospital Alta Complejidad Virgen de la Puerta (HACVP) y Hospital Belén de Trujillo (HBT) durante el periodo de enero-2014 a diciembre-2019. En el análisis de datos se utilizó la prueba Chi-cuadrado para determinar la significancia estadística de asociación en las variables de estudio. Resultados: La edad, uso de antibioticoterapia previa de amplio espectro, uso de sonda vesical, tiempo de uso de sonda vesical y postoperado de cirugía abdominal, se asociaron significativamente (P<0,05) a infección por Pseudomonas aeruginosa multirresistente en pacientes con neumonía asociada a ventilación mecánica de la unidad de cuidados intensivos. El tiempo de exposición de sonda vesical es factor de riesgo para infección por Pseudomonas aeruginosa multirresistente (p<0.001). Conclusiones: El tiempo de uso de sonda vesical por más de 7 días sin recambio de sonda es un factor de riesgo para infección por Pseudomonas aeruginosa multirresistente en pacientes con neumonía asociada a ventilación mecánica.

ABSTRACT Objective: Determine the risk factors for multidrug-resistant Pseudomonas aeruginosa infection in patients with pneumonia associated with mechanical ventilation in the intensive care unit. Material and Methods: An observational, analytical, retrospective, case-control study was carried out in which 84 medical records of patients aged ≥ 18 years with a diagnosis of ventilator-associated pneumonia were selected by simple randomization at the Alta Complejidad Hospital Virgen de la Puerta (HACVP) and Hospital Belén de Trujillo (HBT) during the period from January-2014 to December-2019. In the data analysis, the Chi-square test was used to determine the statistical significance of association in the study variables. Results: Age, use of prior broad-spectrum antibiotic therapy, use of urinary catheter, time of urinary catheter use, and postoperative abdominal surgery were significantly associated (P <0,05) with multidrug-resistant Pseudomonas aeruginosa infection in patients with pneumonia associated with intensive care unit mechanical ventilation. Urinary catheter exposure time is a risk factor for multidrug-resistant Pseudomonas aeruginosa infection (p <0.001). Conclusions: The time of use of the urinary catheter for more than 7 days without change the catheter is a risk factor for infection by multidrug-resistant Pseudomonas aeruginosa in patients with pneumonia associated with mechanical ventilation.

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BACKGROUND: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. OBJECTIVE: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. METHODS: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases. RESULTS: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. CONCLUSION: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

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La guía que se presenta actualmente es una adaptación de la guía de cáncer renal de la Asociación Europea de Urología en su versión más reciente 2020. Se eligió con la metodología ADOLOPMENT tras una evaluación con el instrumento AGREE II

The guideline currently presented is an adaptation of the renal cancer guideline of the European Association of Urology in its most recent version 2020. It was chosen using the ADOLOPMENT methodology after evaluation with the AGREE II instrument.

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Mucopolysaccharidosis type IV A or Morquio syndrome is an uncommon inherited metabolic condition caused by the deficient intralysosomal storage of glycosaminoglycans. Diagnosis is typically based on clinical examination, skeletal radiographs, and histochemical tests in blood cells or fibroblasts. It is characterized by evident skeletal deformities, poor joint mobility, severe growth deficit, occlusal anomalies, and enamel defects. The aim of the present clinical case report is to describe the general oral management provided to a 6-year-old female patient and its corresponding evolution for more than three years.

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8q22.2q22.3 microdeletion syndrome has been described in only seven patients. We present a new case from Colombia. The characteristics of this condition are developmental delay, microcephaly, seizures, and typical facial dysmorphism. We discuss the clinical phenotype of the patient presenting relevant findings like hearing loss and severe epilepsy and the possible relations between the phenotype and the genes involved in the microdeletion. We describe a female with developmental delay, microcephaly, epilepsy, severe short stature, impaired speech, facial dysmorphism, and congenital deafness. A minimal/maximal deletion of 5.238 Mb and 5.374Mb, respectively, at 8q22.2q22.3 was diagnosed using a genome-wide array. The clinical phenotype is similar to the others seven patients previously reported; however, the severity of epilepsy and the concomitant hearing loss is remarkable, characteristics previously observed independently in only two patients. The KCNS2 gene is located in the deleted regions (8q22.2). Therefore it is a possible candidate for explaining the complex neurologic phenotype.

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Endocrine resistance may develop as a consequence of enhanced growth factor signaling. Fibroblast growth factor 2 (FGF2) consists of a low and several high molecular weight forms (HMW-FGF2). We previously demonstrated that antiprogestin-resistant mammary carcinomas display lower levels of progesterone receptor A isoforms (PRA) than B isoforms (PRB). Our aim was to evaluate the role of FGF2 isoforms in breast cancer progression. We evaluated FGF2 expression, cell proliferation, and pathway activation in models with different PRA/PRB ratios. We performed lentiviral infections of different FGF2 isoforms using the human hormone-responsive T47D-YA cells, engineered to only express PRA, and evaluated tumor growth, metastatic dissemination, and endocrine responsiveness. We assessed FGF2 expression and localization in 81 human breast cancer samples. Antiprogestin-resistant experimental mammary carcinomas with low PRA/PRB ratios and T47D-YB cells, which only express PRB, displayed higher levels of HMW-FGF2 than responsive variants. HMW-FGF2 overexpression in T47D-YA cells induced increased tumor growth, lung metastasis, and antiprogestin resistance compared to control tumors. In human breast carcinomas categorized by their PRA/PRB ratio, we found nuclear FGF2 expression in 55.6% of tumor cells. No differences were found between nuclear FGF2 expression and Ki67 proliferation index, tumor stage, or tumor grade. In low-grade tumor samples, moderate to high nuclear FGF2 levels were associated to carcinomas with low PRA/PRB ratio. In conclusion, we show that HMW-FGF2 isoforms are PRB targets which confer endocrine resistance and are localized in the nuclei of breast cancer samples. Hence, targeting intracellular FGF2 may contribute to overcome tumor progression.

Assuntos

RESUMO

Galactosialidosis (GS) is a rare form of lysosomal storage disease that involves a broad spectrum of skeletal and soft tissue abnormalities. We report here on a 4-year 7-month-old boy with mild mental retardation, exhibiting multiple caries cavities and associated infectious foci and macroglossia. A huge abdominal enlargement due to peritoneal ascites was evident. Behavioral management and patient positioning on the dental chair represented a true challenge. The patient was treated under general anesthesia. However, life-threatening postoperative complications occurred because of the impossibility of extubating the patient. A very careful preanesthetic assessment is crucial in children affected by general conditions associated with airway anomalies, such as GS.

RESUMO

La prostatectomía radical (PR), es el procedimiento quirúrgico de elección cuando se trata de dar manejo con intención curativa al cáncer de próstata localizado. Fue el primer tratamiento quirúrgico descrito para el cáncer de próstata y ha sido realizado por más de 100 años. Tiene como ventaja importante frente a la radioterapia el permitir la estadificación precisa con el estudio patológico del espécimen quirúrgico; sin embargo, tiene algunas desventajas como la necesidad de hospitalización y recuperación post operatoria intrahospitalaria, la posibilidad de una resección incompleta y el riesgo de incontinencia urinaria y de disfunción eréctil, entre otras.1­3 La frecuencia de complicaciones y secuelas descrita en la literatura es variable, con amplios rangos según las diferentes series y autores disponibles.

Radical prostatectomy (PR) is the surgical procedure of choice when it comes to managing localized prostate cancer with curative intent. It was the first surgical treatment described for prostate cancer and has been performed for over 100 years. However, it has some disadvantages such as the need for hospitalization and in-hospital post-operative recovery, the possibility of incomplete resection and the risk of urinary incontinence and erectile dysfunction, among others.1-3 The frequency of complications and sequelae described in the literature is variable, with wide ranges according to the different series and authors available.

Assuntos