Showing papers in "Revista De Investigacion Clinica in 2019"

Respiratory Impact of Electronic Cigarettes and Low-Risk Tobacco

Abstract: Electronic cigarettes, handheld devices that generate an aerosol that may contain nicotine by heating a solution or e-liquid, have been increasingly used especially in the young population. The aerosol's composition is determined by temperature, and by the substances contained in the heated liquid: glycerin, propylene glycol, nicotine in variable concentrations, flavoring agents, and other non-nicotine compounds. >80 compounds (including known toxics, e.g., formaldehyde, acetaldehyde, metallic nanoparticles, and acrolein) have been found in e-liquid and aerosols. Airway irritation, mucus hypersecretion, and inflammatory response, including systemic changes, have been observed after the exposure to e-cigarettes, leading to an increase in respiratory symptoms and changes in respiratory function and the host defense mechanisms. E-cigarette has been linked with an increase of symptoms in individuals with asthma, cystic fibrosis, and chronic obstructive pulmonary disease. One of the major concerns in public health is the rise in e-cigarette experimentation among never-smokers, especially children and adolescents, which leads to nicotine addiction and increases the chances of becoming with time a conventional smoker. There is an urgent need to regulate e-cigarettes and electronic nicotine delivery systems, at least with the same restrictions to those applied to tobacco products, and not to consider them as harmless products.

Smoking cessation treatments: Current psychological and pharmacological options

Abstract: Background: Smoking is considered an epidemic, indeed, one of the most important public health problems worldwide. It is also the most significant preventable cause of death, of a high number of premature deaths, and avoidable chronic diseases. It is considered an enormous economic burden for the world. Objective: To provide an overview of smoking-cessation treatments, including pharmacological and psychological options, and to gather current scientific evidence available on them. Methods: Research included reviewing publications from 2007-2018 in four databases using algorithms related to bupropion, varenicline, nicotine replacement therapy, smoking cessation, psychological treatment, motivational interview, cognitive-behavioral therapy and clinical guidelines for smoking treatment. Meta-analyses or systematic reviews and randomized or quasirandomized trials were selected. We also included clinical guidelines for smoking treatment from Mexico and other countries. Results: After refining the search, 37 articles met the criteria and were included in the review. The results were grouped by type of intervention. Conclusions: It is necessary to conduct research on combinations of both kinds of treatment with an integral, multidisciplinary vision. Current standard for smoking cessation is a combined psychological and pharmacological treatment. (REV INVEST CLIN. 2019;71:7-16)

Role of genetic susceptibility in nicotine addiction and chronic obstructive pulmonary disease.

Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries. Although cigarette smoking is the major risk factor, only 10-20% of smokers develop COPD. The extent of cigarette smoking (pack-years and smoking duration) accounts for only 15% of the variation in lung function, indicating that differences in susceptibility to COPD must exist. We provide an overview of the complexity of nicotine addiction and COPD, with special attention to the involvement of genetic factors. The following aspects are discussed in the present article: (1) epidemiology in Mexico and (2) a review of the published literature on genetic association studies using the National Center for Biotechnology Information database of the United States as a search tool. COPD is unique among complex genetic diseases where an environmental risk factor is known and the level of exposure can be documented with some precision. The high morbidity and mortality associated with COPD and its chronic and progressive nature has prompted the use of molecular genetic studies to identify susceptibility factors for the disease. Biomedical research has a remarkable set of tools to aid in the discovery of genes and polymorphisms. We present a review of the most relevant genetic associations in nicotine addiction and COPD.

Astemizole, an inhibitor of ether-à-go-go-1 potassium channel, increases the activity of the tyrosine kinase inhibitor gefitinib in breast cancer cells.

Abstract: espanolAntecedentes: la expresion y la actividad del canal de potasio eter-a-go-go-1 (EAG1) estan fuertemente relacionadas con la carcinogenesis y la progresion tumoral, que pueden explotarse con fines terapeuticos. La actividad de EAG1 puede reducirse evitando su fosforilacion con inhibidores de la quinasa del receptor del factor de crecimiento epidermico (EGFR) y con astemizol, que bloquea el poro del canal y regula negativamente su expresion genica. Objetivo: Nuestro objetivo fue estudiar el posible efecto antiproliferativo cooperativo del inhibidor de EGFR gefitinib y el astemizol bloqueador de EAG1, en celulas de cancer de mama. Materiales y metodos: las celulas se caracterizaron por inmunocitoquimica. Las concentraciones inhibitorias se determinaron mediante analisis de regresion no lineal utilizando curvas de dosis-respuesta. La naturaleza del efecto farmacologico se evaluo mediante la ecuacion de indice de combinacion, mientras que el analisis del ciclo celular se estudio mediante citometria de flujo. Resultados: el astemizol y el gefitinib inhibieron la proliferacion celular de manera dependiente de la concentracion, con valores de concentracion inhibitoria (CI50) de 1.72 µM y 0.51 µM, respectivamente. Todas las combinaciones dieron como resultado un efecto antiproliferativo sinergico. La combinacion de astemizol y gefitinib disminuyo el porcentaje de celulas en las fases G2 / M y S, mientras que aumento la acumulacion en G0 / G1 del ciclo celular. Conclusiones: el astemizol y el gefitinib inhibieron sinergicamente la proliferacion en las celulas de cancer de mama que expresan tanto EGFR como EAG1. Nuestros resultados sugieren que el tratamiento combinado aumento la muerte celular al enfocarse en la actividad oncogenica de EAG1. EnglishBackground: Expression and activity of the potassium channel ether-a-go-go-1 (EAG1) are strongly related to carcinogenesis and tumor progression, which can be exploited for therapeutic purposes. EAG1 activity may be reduced by preventing its phosphorylation with epidermal growth factor receptor (EGFR) kinase inhibitors and by astemizole, which blocks the channel pore and downregulates its gene expression. Objective: We aimed to study the potential cooperative antiproliferative effect of the EGFR inhibitor gefitinib and the EAG1-blocker astemizole, in breast cancer cells. Materials and Methods: The cells were characterized by immunocytochemistry. Inhibitory concentrations were determined by non-linear regression analysis using doseresponse curves. The nature of the pharmacological effect was evaluated by the combination index equation while cell cycle analysis was studied by flow cytometry. Results: Astemizole and gefitinib inhibited cell proliferation in a concentration-dependent manner, with inhibitory concentrations (IC 50) values of 1.72 µM and 0.51 µM, respectively. All combinations resulted in a synergistic antiproliferative effect. The combination of astemizole and gefitinib diminished the percentage of cells in G2/M and S phases, while increased accumulation in G0/G1 of the cell cycle. Conclusions: Astemizole and gefitinib synergistically inhibited proliferation in breast cancer cells expressing both EGFR and EAG1. Our results suggest that the combined treatment increased cell death by targeting the oncogenic activity of EAG1. (REV INVEST CLIN. 2019;71:186-94)

Association of vitamin d with mild cognitive impairment and alzheimer's dementia in older mexican adults.

Abstract: espanolAntecedentes: se ha propuesto que la vitamina D ayuda a reducir la acumulacion de β-amiloide-42 cerebral mediante la estimulacion inmune innata y la activacion de la fagocitosis. Se ha establecido una asociacion entre los niveles bajos de vitamina D y la demencia de Alzheimer (EA). Determinamos la asociacion entre vitamina D, deterioro cognitivo leve (DCL) y EA en adultos mayores mexicanos (> 65 anos) Metodos: estudio transversal realizado en la clinica de memoria de un hospital de nivel terciario de la Ciudad de Mexico. Evaluamos sujetos con DCL, EA y cognicion normal (NC) con niveles sericos de vitamina D [25 (OH) D] disponibles (ultimos 6 meses). Se asignaron tres categorias de acuerdo con los niveles de 25 (OH) D: suficiencia (> 30 ng / ml), insuficiencia (21-29 ng / ml) y deficiencia (≤ 20 ng / ml). Se utilizo estadistica descriptiva, medias y desviaciones estandar. Se realizaron analisis de regresion logistica ajustados por edad, sexo y nivel educativo Resultados: Evaluamos a 208 pacientes. La edad media fue 79 ± 1 ano, el 65% (n = 136) eran mujeres; y el nivel educativo medio fue de 6,7 ± 2,3 anos. Treinta y un sujetos (14%) tenian NC; 42% (n = 88) tenia DCL; y el 43% (n = 89) tenia EA. La prevalencia de la deficiencia de vitamina D fue del 54%, mas frecuente en el grupo de EA (64%) seguido por los grupos de DCL (59%) y NC (13%) (p EnglishBackground: It has been proposed that Vitamin D helps reduce the accumulation of cerebral β-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer’s dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (> 65 years). Methods: Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (> 30 ng/mL), insufficiency (21-29 ng/mL), and defi- ciency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed. Results: We evaluated 208 patients. Mean age was 79 ± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p

Oxidative stress, telomere length, and frailty in an old age population.

Abstract: espanolAntecedentes: Una poblacion global que envejece requiere centrarse en los factores de riesgo del envejecimiento no saludable, la medicina preventiva y el manejo de enfermedades cronicas. La identificacion de resultados adversos para la salud en los adultos mayores se ha abordado mediante la caracterizacion de la fragilidad como un sindrome biologico. En este campo, el estres oxidativo y la longitud de los telomeros se han sugerido como biomarcadores del envejecimiento. Objetivo: El objetivo del estudio fue estudiar la asociacion del estres oxidativo, la longitud de los telomeros y la fragilidad en una poblacion de edad avanzada. Metodos: Realizamos un estudio transversal basado en datos de 2015 de 202 miembros de una cohorte de adultos mayores (n = 202; razon de genero F / M: 133/69; edad media: 69,89 ± 7,39 anos). Las especies reactivas de oxigeno se midieron por diacetato de diclorofluoresceina y peroxidacion de lipidos por malondialdehido. La longitud de los telomeros se determino mediante la reaccion cuantitativa en cadena de la polimerasa con SYBR Green Master Mix Resultados: El analisis estadistico mostro una asociacion entre la longitud de los telomeros y la fragilidad, pero no entre el estres oxidativo y la longitud o fragilidad de los telomeros. Conclusiones: La longitud de los telomeros podria eventualmente usarse como un marcador para diferenciar entre el envejecimiento saludable y no saludable expresado por el fenotipo de fragilidad; El estres oxidativo parecia simplemente un proceso biologico de envejecimiento. EnglishBackground: A global aging population requires focusing on the risk factors for unhealthy aging, preventive medicine, and chronic disease management. The identification of adverse health outcomes in older adults has been addressed by the char- acterization of frailty as a biological syndrome. In this field, oxidative stress and telomere length have been suggested as biomarkers of aging. Objective: The objective of the study was to study the association of oxidative stress, telomere length, and frailty in an old age population. Methods: We conducted a cross-sectional study based on 2015 data from 202 members of a cohort of older adults (n = 202; F/M gender ratio: 133/69; mean age: 69.89 ± 7.39 years). Reactive oxygen species were measured by dichlorofluorescein diacetate and lipid peroxidation by malondialdehyde. Telomere length was determined using quantitative polymerase chain reaction with SYBR Green Master Mix. Results: Statistical analysis showed an association between telomere length and frailty but no association between oxidative stress and telomere length or frailty. Conclusions: Telomere length could eventually be used as a marker to differentiate between healthy and unhealthy aging as expressed by frailty phenotype; oxidative stress seemed merely a biological process of aging. (REV INVEST CLIN. 2019;71:393-401)

SMALLa AIRWAY DISEASE IN COPD ASSOCIATED TO BIOMASS EXPOSURE.

Abstract: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world's population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Piperacillin/Tazobactam in Continuous Infusion versus Intermittent Infusion in Children with Febrile Neutropenia

Abstract: espanolAntecedentes: la neutropenia febril (FN) es una complicacion comun en ninos que reciben quimioterapia para el cancer. Objetivo: El objetivo de este estudio fue evaluar la eficacia clinica de la infusion continua versus intermitente de piperacilina / tazobactam (TZP) en pacientes pediatricos neutropenicos febriles. Metodos: Este es un ensayo clinico aleatorizado controlado no cegado. El grupo elegible consistio en pacientes hemato-oncologicos con FN que eran candidatos para recibir TZP. Los pacientes fueron asignados al azar a uno de dos grupos: el Grupo 1 recibio tratamiento con antibioticos a traves de una infusion intravenosa intermitente de TZP 300 mg / kg / dia basado en piperacilina, dividido en cuatro dosis, sin exceder los 16 g / dia; El grupo 2 recibio una dosis inicial de carga de TZP de 75 mg / kg de infusion durante 30 minutos, y luego una infusion continua de TZP de 300 mg / kg / dia a traves de la via central con bomba durante 24 h. Resultados: Hubo 176 episodios que pudieron evaluarse, 100 en el Grupo 1 y 76 en el Grupo 2. No hubo diferencias estadisticamente significativas en el fracaso del tratamiento en el grupo experimental (infusion continua) en comparacion con el grupo intermitente, 21% versus 13% ( p = 0,15). El aumento en la reduccion del riesgo absoluto fue del 0.08% (intervalo de confianza del 95% 0.12-0.30), y el numero necesario para tratar fue 12.4. Un paciente en cada grupo fallecio. Conclusiones: No hubo diferencias en la resolucion de la fiebre, la tasa de curacion clinica o la mortalidad al comparar la infusion continua con la infusion intermitente de TZP. EnglishBackground: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/ tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion. (REV INVEST CLIN. 2019;71:283-90)

Basic and clinical insights in catecholaminergic (familial) polymorphic ventricular tachycardia

Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

Clinical and biomedical applications of surface plasmon resonance systems.

Abstract: Surface plasmon resonance (SPR)-based biosensors offer superior analytical features such as simplicity, sensitivity, and specificity when compared to conventional methods in clinical analyses. In addition, they deliver real-time monitoring of label-free analytes with high-throughput approaches requiring little sample pretreatment that allows the analysis of virtually every clinical sample type to determine the amount and/or activity of any molecule of interest. Accordingly, SPR emerges as a novel, efficient, powerful, and relatively low-cost alternative tool for routine clinical analysis, opening also new horizons for developments in personalized medicine applied to diagnostics or therapeutics' monitoring.

II. The Research Ethics Involving Vulnerable Groups

Abstract: Vulnerability in research occurs when the participant is incapable of protecting his or her interests and therefore, has an increased probability of being intentionally or unintentionally harmed. This manuscript aims to discuss the conditions that make a group vulnerable and the tools and requirements that can be used to reduce the ethical breaches when including them in research protocols. The vulnerability can be due either to an inability to understand and give informed consent or to unequal power relationships that hinder basic rights. Excluding subjects from research for the only reason of belonging to a vulnerable group is unethical and will bias the results of the investigation. To consider a subject or group as vulnerable depends on the context, and the investigator should evaluate each case individually.

POLYMORPHISMS IN β-ADRENERGIC RECEPTORS ARE ASSOCIATED WITH INCREASED RISK TO HAVE A POSITIVE HEAD-UP TILT TABLE TEST IN PATIENTS WITH VASOVAGAL SYNCOPE.

Abstract: espanolAntecedentes: el sincope vasovagal (VVS) es una condicion clinica frecuente en la que parece estar implicado un fondo genetico. Teniendo en cuenta que los receptores adrenergicos (AR) pueden desempenar un papel en VVS, el presente estudio tiene como objetivo principal determinar si lospolimorfismos del genα- y β-AR ( ADRA y ADRB ) estan asociados con un mayor riesgo de tener una cabeza positiva de inclinacion vertical (HUTT) en pacientes con VVS. Metodos: Nueve polimorfismos en ADRA1A (rs1048101, rs1383914, rs574584 y rs573542), ADRB1 (rs1801252 y rs1801253), ADRB2 (rs1042713 y rs1042714) y ADRB3 (rs4994) los genes se analizaron usando el ensayo de genotipado TaqMan de exonucleasa 5 'en un grupo de 134 pacientes con VVS. Resultados: bajo diferentes modelos, rs1801252 (OR = 8.63, IC 95%: 0.95-78.72, P recesivo = 0.02), rs1042713 (OR = 1.94, IC 95%: 1.02-3.66, aditivo P= 0.04) y rs4994 ( OR = 2.46, IC 95%: 1.01-6.01, P dominante = 0.042 y OR = 2.62, IC 95%: 1.04-6.63, P sobre-dominante = 0.03) los polimorfismos se asociaron con un mayor riesgo de HUTT positivo. Todos los modelos fueron ajustados por covariables estadisticamente significativas. Conclusion: estos resultados sugieren que algunos polimorfismos de los genes β-AR podrian contribuir a una prueba de inclinacion positiva en pacientes con VVS. EnglishBackground: Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and β-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5’ exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. Results: Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. Conclusion: These results suggest that some polymorphisms of the β-AR genes could contribute to a positive tilt test in patients with VVS. (REV INVEST CLIN. 2019;71:124-32)

Controversies and limitations in the diagnosis of chronic obstructive pulmonary disease.

Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. While the cut-off point to define airflow obstruction has been controversial, it is widely accepted that the spirometry test is vital, as well as performing it after using a bronchodilator. The 6-second spirometry and the forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV1/FEV6) have demonstrated validity for defining obstruction, and it would be advisable to incorporate them in the definitions of obstruction. Another relevant issue is that spirometry with borderline obstruction can vary over time, changing to above or below the cut-off point. Thus, surveillance should be considered over time, repeating the spirometry to have a greater certainty in the diagnosis. The objective of this article was to conduct an in-depth review of the controversies in the diagnosis of COPD. During the past years, COPD definition has been updated in different times; however, it is now considered more as a complex syndrome with systemic participation, requiring a multidimensional assessment, and not only a spirometry.

Frequency of depression and anxiety symptoms in mexican patients with rheumatic diseases determined by self-administered questionnaires adapted to the spanish language.

Abstract: Background The frequency of depression and anxiety symptoms in Spanish-speaking patients suffering from rheumatic conditions is unknown when using self-administered detection tools. Methods A single-center, cross-sectional survey including 413 patients (341 women) with well-defined rheumatic diseases was conducted. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder (GAD)-7 questionnaires were used to detect depression and anxiety symptoms, respectively. Results A total of 193 patients (46.7%) reported depression symptoms, and increased PHQ-9 scores were more frequently observed in women than in men (23% vs. 13%; p = 0.038), particularly in association with osteoarthritis, fibromyalgia, Sjogren's syndrome, and osteoporosis. From 88 patients (21.3%) with PHQ-9 scores ≥ 10 points (moderate-to-severe depression symptoms), 27 (30.6%) were previously diagnosed to have depression and only four were under antidepressant treatment. Anxiety symptoms were observed in 168 patients (40.6%) and classified as moderate-to-severe by elevated GAD-7 scores in 68 subjects (16.4%). Of them, 12 (17.6%) were previously diagnosed with GAD, but only 4 (5.8%) were under therapy. Conclusions An unexpected and unusually high frequency of undiagnosed depression and anxiety symptoms was found in rheumatic patients. Self-administered screening tools adapted to the Spanish language are useful and may help clinicians to suspect these conditions.

Real-world evidence of dengue burden on hospitals in mexico: insights from the automated subsystem of hospital discharges (saeh) database.

Abstract: espanolAntecedentes: la incidencia del dengue en Mexico ha aumentado en las ultimas decadas. Se ha sugerido que los brotes de dengue pueden comprometer la calidad del tratamiento en los hospitales. Objetivo: El objetivo del estudio fue cuantificar la carga impuesta por el dengue en los servicios hospitalarios en Mexico. Metodos: Analizamos 19.2 millones de registros contenidos en la base de datos de servicios hospitalarios del Ministerio de Salud de Mexico entre 2008 y 2014. El numero de ingresos por dengue se comparo con otras hospitalizaciones potencialmente prevenibles. Los departamentos hospitalarios se clasificaron para reflejar la actividad relacionada con el dengue como departamentos de actividad alta de dengue (HDA), baja actividad de dengue (LDA) o cero dengue, y se evaluo el impacto de la actividad del dengue en la mortalidad hospitalaria general en los departamentos de HDA. Resultados: el dengue fue la causa de mas ingresos hospitalarios que la mayoria de las afecciones agudas y cronicas prevalentes potencialmente evitables y otras enfermedades infecciosas. En los departamentos de HDA, se encontro que la carga de pacientes con dengue es un factor de riesgo significativo para la mortalidad general en el hospital. Hubo una tasa de letalidad por dengue aproximadamente dos veces mayor en los departamentos de LDA versus HDA, independientemente de la gravedad del dengue. Conclusiones: Este estudio confirma que el dengue es una causa importante de hospitalizacion en Mexico y destaca el impacto de la actividad del dengue no solo en la tasa de letalidad de casos de dengue sino tambien en la mortalidad general en el hospital. EnglishBackground: The incidence of dengue in Mexico has increased in recent decades. It has been suggested that dengue outbreaks may compromise treatment quality in hospitals. Objective: The objective of the study was to quantify the burden imposed by dengue on hospital services in Mexico. Methods: We analyzed 19.2 million records contained in the database of hospital services of the Mexican Ministry of Health between 2008 and 2014. The number of admissions due to dengue was compared to other potentially preventable hospitalizations. Hospital departments were categorized to reflect denguerelated activity as high dengue activity (HDA), low dengue activity (LDA), or zero dengue activity departments, and the impact of dengue activity on general in-hospital mortality in HDA departments was assessed. Results: Dengue was the cause of more hospital admissions than most of the potentially preventable prevalent acute and chronic conditions and other infectious diseases. In HDA departments, dengue patient load was found to be a significant risk factor for overall in-hospital mortality. There was an approximately two-fold higher dengue case-fatality rate in LDA versus HDA departments, irrespective of dengue severity. Conclusions: This study confirms that dengue is an important cause of hospitalization in Mexico and highlights the impact of dengue activity not only on dengue case-fatality rate but also on the overall in-hospital mortality. (REV INVEST CLIN. 2019;71:168-77)

Clinical characteristics of primary extranodal versus nodal diffuse large b-cell lymphoma: a retrospective cohort study in a cancer center.

Abstract: espanolAntecedentes: el resultado de los pacientes con linfoma de celulas B grandes extranodal primario difuso (PE-DLBCL) varia segun el sitio primario involucrado. DLBCL primario gastrointestinal, mamario, oseo, craneofacial y testicular son manifestaciones extranodales raras de DLBCL. Objetivo: El objetivo del estudio fue describir el curso clinico de los pacientes con enfermedad de PE-DLBCL en un centro de cancer de referencia. Resultados: de 637 pacientes, se considero que 51 (8,77%) tenian PE-DLBCL (25 gastrointestinales, 12 craneofaciales, 6 de mama, 5 de hueso y 3 con DLBCL testicular primario). La remision completa fue mayor en todos los sitios de PE-DLBCL (100% en testicular, 92,6% craneofacial, 83,3% de mama, 80% de hueso y 80% gastrointestinal) en comparacion con 73,3% en DLBCL nodal. Aunque 2 casos con PE-DLBC de mama recayeron, lograron una respuesta completa con quimioterapia. La supervivencia general a los 5 anos fue del 100%, 80%, 78%, 58%, 58% y 62% para pacientes con DLBCL primario de mama, hueso primario, gastrointestinal, craneofacial primario, testicular primario y ganglionar, respectivamente. Conclusiones: los PE-DLBCL constituyen sitios primarios raros de trastornos linfoproliferativos en la mayoria de los casos, con enfermedad localizada y buen pronostico. Requieren una quimioinmunoterapia combinada con radioterapia en la mayoria de los casos para mejorar la enfermedad local y sistemica. EnglishBackground: The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. Objective: The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. Results: From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. Conclusions: PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease. (REV INVEST CLIN. 2019;71:349-58)

Fasting insulin and alanine amino transferase, but not fgf21, were independent parameters related with irisin increment after intensive aerobic exercising.

Abstract: espanolAntecedentes: Irisin es una proteina escindida de la proteina 5 que contiene el dominio de fibronectina tipo III y se ha implicado en los efectos beneficiosos del ejercicio. Sin embargo, se desconoce que factores contribuyen al incremento de irisina despues del ejercicio intensivo en humanos. Este estudio tuvo como objetivo evaluar factores independientes relacionados con la irisina serica despues de 2 semanas de actividad fisica supervisada en mujeres jovenes sedentarias sanas. Diseno y metodos: desarrollamos un estudio comparativo, intervencionista, longitudinal y prospectivo en un centro de salud especializado de tercer nivel. Entre marzo de 2010 y agosto de 2011, se reclutaron 82 mujeres adultas jovenes sedentarias, sin enfermedades cronicas o tratamientos medicos regulares. Un total de 38 mujeres cumplieron los criterios de seleccion, y las concentraciones de irisina se cuantificaron antes y despues de la intervencion. Se evaluaron factores independientes relacionados con el incremento de irisina de acuerdo con la intensidad de actividad fisica leve a moderada y vigorosa. Se realizo una prueba supervisada de ejercicio en la cinta de correr siguiendo el protocolo de Bruce de lunes a viernes durante 2 semanas. Ademas, se tomaron medidas antropometricas y se midieron el factor de crecimiento de fibroblastos 21 (FGF21), glucosa, insulina y transaminasas hepaticas. Resultados: la intensidad del ejercicio se relaciono directamente conlos niveles sericos deirisina ( p = 0.02) y FGF21 ( p = 0.01). Sin embargo, no se confirmo una relacion independiente y significativa entre FGF21 e irisina. Se encontro una nueva asociacion entre alanina aminotransferasa (ALT) e irisina, que muestra una correlacion positiva y significativa ( r = 0.37, p = 0.02). La asociacion fue particularmente fuerte con una mayor intensidad de ejercicio aerobico ( r = 0.64, p = 0.01). El modelo de regresion lineal ajustado por glucosa e indice de masa corporal confirmo una asociacion independiente entre ALT e irisina y tambien entre insulina e irisina (R² ajustado = 0,12, p= 0.04). Dicha asociacion aumento despues de agrupar en intensidad de actividad fisica moderada a vigorosa (R² ajustado = 0.46, F = 4.7, p = 0.03). Conclusiones: los niveles sericos de irisina y FGF21 aumentaron significativamente despues de 2 semanas de actividad fisica supervisada. Sin embargo, solo la insulina en ayunas y ALT, pero no FGF21, fueron parametros independientes que explican el incremento de irisina, principalmente despues de un ejercicio moderado a vigoroso. EnglishBackground: Irisin is a protein cleaved from fibronectin type III domain-containing protein 5 and has been implicated in the beneficial effects of exercise. However, it is unknown which factors contribute to irisin increment after intensive exercising in humans. This study aimed to assess independent factors related with serum irisin after 2 weeks of supervised physical activity in young sedentary healthy women. Design and Methods: We developed a comparative, interventional, longitudinal, and prospective study at a third-level specialty health center. Between March 2010 and August 2011, 82 sedentary young adult women, without chronic diseases or regular medical treatments, were recruited. A total of 38 women fulfilled selection criteria, and irisin concentrations were quantified before and after the intervention. Independent factors related with irisin increment were evaluated according to mild to moderate and vigorous intensity of physical activity. A supervised treadmill exercise test following the Bruce’s protocol was conducted from Monday to Friday during 2 weeks. In addition, anthropometric measurements were taken, and fibroblast growth factor 21 (FGF21), glucose, insulin, and liver transaminases were measured. Results: Intensity of exercising was directly related to irisin (p = 0.02) and FGF21 (p = 0.01) serum levels. However, an independent and significant relationship between FGF21 and irisin was not confirmed. A novel association was found between alanine aminotransferase (ALT) and irisin, showing a positive and significant correlation (r = 0.37, p = 0.02). The association was particularly strong with higher intensity of aerobic exercising (r = 0.64, p = 0.01). Linear regression model adjusted for glucose and body mass index confirmed an independent association between ALT and irisin and also between insulin and irisin (adjusted R² = 0.12, p = 0.04). Such association increased after grouping in moderate to vigorous physical activity intensity (adjusted R² = 0.46, F = 4.7, p = 0.03). Conclusions: Serum irisin and FGF21 levels significantly increased after 2 weeks of supervised physical activity. However, only fasting insulin and ALT, but not FGF21, were independent parameters explaining irisin increment, mainly after moderate to vigorous exercising. (REV INVEST CLIN. 2019;71:133-40)

Chronic obstructive pulmonary disease: perspectives for primary health care.

Abstract: espanolAntecedentes: la enfermedad pulmonar obstructiva cronica (EPOC) se ha convertido en un importante desafio para la salud en todo el mundo debido a su creciente incidencia y mortalidad, que tienen graves repercusiones para los sistemas de atencion de la salud. Metodos: Realizamos una revision de los esfuerzos internacionales para controlar la EPOC en atencion primaria. Resultados: La OMS creo la declaracion de Alma-Ata que establecio por primera vez el acceso a la atencion medica como un derecho humano. Este precepto condujo a la implementacion de numerosos programas que incluyen un enfoque practico para la salud pulmonar y variantes en varios paises; esquemas disenados para centralizar la atencion medica; y recursos para mejorar la atencion de las enfermedades respiratorias mediante la adaptacion de enfoques a las necesidades de atencion medica de las poblaciones locales. La atencion primaria de salud respiratoria debe incluir acciones para la deteccion oportuna, la educacion sanitaria y el tratamiento dirigido, pero el desafio para todos los sistemas de salud es garantizar que sus programas funcionen adecuadamente, ya que aun muestran deficiencias en cuanto a su aplicacion. Conclusiones: Llegamos a la conclusion de que ofrecer atencion primaria de salud basada en modelos que combinen diagnosticos oportunos con un tratamiento adecuado puede influir positivamente en el curso de la EPOC al tratar las primeras etapas, lo que ralentiza su progresion. Sin embargo, una educacion mas extensa y una difusion mas amplia de informacion son necesarias para lograr este objetivo. EnglishBackground: Chronic obstructive pulmonary disease (COPD) has become a major health challenge worldwide due to its increasing incidence and mortality, which have serious repercussions for health-care systems. Methods: We conducted a review of international efforts to control COPD in primary care. Results: The WHO created the Alma-Ata declaration which established for the first time, access to health care as a human right. This precept led to the implementation of numerous programs including practical approach to Lung Health and variants in several countries; schemes designed to centralize medical care; and resources to improve attention of respiratory diseases by adapting approaches to the health-care needs of local populations. Primary respiratory health care should include actions for timely detection, health education, and targeted treatment, but the challenge for all health systems is to ensure that their programs function adequately, for they still show shortcomings in terms of their application. Conclusions: We conclude that offering primary health care based on models that combine opportune diagnoses with suitable treatment can positively influence the course of COPD by treating early stages, thus slowing its progression. However, more extensive education and broader dissemination of information are necessary to achieve this goal. (REV INVEST CLIN. 2019;71:55-63)

Deriving Primary Cancer Cell Cultures for Personalized Therapy

Abstract: Cancer is the second-leading cause of death in the world, accounting for one out of six deaths. Consequently, there is an urgent need for new and more effective therapeutic options as well as drug screening methods. Immortal, "stable" cancer cell lines have been employed since the past century to assess drug response but face several disadvantages. They often accumulate new genetic aberrations due to long-term culture and lack the indisputable heterogeneity of solid tumors, therefore, compromising the recapitulation of molecular features from parental tumors. Primary cancer cells have emerged as an attractive alternative to commercial cell lines since they can preserve such properties more closely. Here, we provide an overview of the basic concepts underlying generation and characterization of primary cell cultures from tumor samples. We emphasize the advantages and disadvantages of using these types of cancer cell cultures, and we make a comparison with other types of cultures used for personalized therapy. Finally, we consider the use of primary cancer cell cultures in personalized therapy as a means to improve drug response prediction and therapeutic outcomes.

Exploratory analysis of polygenic risk scores for psychiatric disorders: applied to dual diagnosis.

Abstract: espanolAntecedentes: la concurrencia de trastornos por uso de sustancias (TUS) es alta en personas con enfermedades psiquiatricas; Mas importante aun, las personas con ambos trastornos (diagnostico dual) tienen sintomas mas graves. Se han propuesto trastornos psiquiatricos para compartir una susceptibilidad genetica con los TUS. Para explorar esta susceptibilidad genetica compartida, analizamos si alguna de las puntuaciones de riesgo poligenico (PRS) para los trastornos psiquiatricos podria estar asociada al diagnostico dual en pacientes con esquizofrenia (SCZ) o trastorno bipolar (BD). Metodos: Se incluyeron 192 individuos de ascendencia mexicana: 72 con SCZ, 53 con BD y 67 controles no relacionados sin trastornos psiquiatricos. Derivamos calculos de PRS para trastornos del espectro autista, trastorno de deficit de atencion / hiperactivo, BD, depresion mayor y SCZ utilizando estadisticas resumidas de asociacion de genoma previamente publicadas. Resultados: Encontramos que el diagnostico dual tenia una susceptibilidad genetica compartida con el trastorno depresivo mayor (MDD) y SCZ; Ademas, en individuos con BD, PRS podria predecir el diagnostico dual para MDD. Conclusiones: Nuestros resultados refuerzan la nocion de que las personas con diagnostico dual tienen una mayor susceptibilidad genetica a desarrollar ambos trastornos. Sin embargo, se requieren analisis de muestras de mayor tamano para aclarar aun mas como predecir riesgos a traves de PRS dentro de diferentes poblaciones. EnglishBackground: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations. (REV INVEST CLIN. 2019;71:321-9)

Treatment strategies and outcome of parvovirus b19 infection in kidney transplant recipients: a case series and literature review of 128 patients.

Abstract: espanolAntecedentes: no existe un tratamiento antiviral especifico para la infeccion por parvovirus B19 (PVB19). Objetivo: El objetivo de este estudio fue estudiar el tratamiento y el resultado de la infeccion por PVB19 en receptores de trasplante de rinon (KTR) en nuestra institucion, y los casos publicados en la literatura medica. Metodos: Realizamos una revision retrospectiva de la infeccion por PVB19 en KTR en un centro medico academico durante un periodo de 16 anos y resumimos los datos sobre su tratamiento y resultados en 120 KTR en la literatura medica. Resultados: en nuestra cohorte de ocho pacientes, la mediana del tiempo hasta el inicio de la enfermedad PVB19 fue de 7,2 semanas despues del trasplante. Todos los pacientes tenian anemia aregenerativa grave (hemoglobina media (Hb) de 6.2 ± 1.0 g / dl); todos fueron tratados con una reduccion en su regimen inmunosupresor y la administracion de una dosis unica de inmunoglobulina intravenosa (IGIV) (dosis total media de 0,87 ± 0,38 g / kg). La mediana del tiempo hasta la mejoria de la anemia (Hb> 10 g / dl) fue de 3 semanas despues del tratamiento. No se documentaron recurrencias durante el seguimiento (mediana de 25 meses). Entre 128 pacientes (incluida nuestra cohorte de 8 y 120 informados en la literatura), las estrategias terapeuticas incluyeron: 43% de IGIV sola, 39% de IgIV y inmunosupresion reducida, 9% de reduccion de inmunosupresion y 9% de terapia conservadora. Se observaron recaidas clinicas en el 35% de los 71 casos reportados. Conclusiones: en KTR, la disminucion de la inmunosupresion y la administracion de dosis bajas de inmunoglobulina no parecen ser peores que la dosis estandar en la infeccion por PVB19. EnglishBackground: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. Objective: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. Methods: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. Results: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. Conclusions: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection. (REV INVEST CLIN. 2019;71:265-74)

Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity.

Abstract: espanolAntecedentes: el consumo excesivo de azucar agregado se asocia con obesidad, enfermedad del higado graso no alcoholico (NAFLD) y resistencia a la insulina (IR). Objetivo: El objetivo del estudio fue estudiar la proteina de union al factor de crecimiento similar a la insulina 1 (IGFBP-1) y la NAFLD y su relacion con el consumo de fructosa en ninos con obesidad. Metodos: se realizo un estudio transversal en ninos de 6 a 11 anos con obesidad. Se evaluaron mediciones antropometricas, consumo de fructosa, glucosa, perfil lipidico, insulina e IGFBP-1; Se utilizo la evaluacion del modelo homeostatico de IR (HOMA-IR). NAFLD fue evaluado por ultrasonido. Resultados: Estudiamos a 83 ninos con una edad media de 9.2 ± 1.3 anos. Alrededor del 93% de las ninas presentaron IR y niveles mas bajos de IGFBP-1 (p = 0,0001). El grupo con los niveles mas bajos de IGFBP-1 tuvo mayor HOMA-IR (p = 0.000002); IGFBP-1 se asocio con el consumo de fructosa (r = −0.25; p = 0.03), indice de masa corporal (IMC) (r = −0.42; p = 0.02) y HOMA-IR (r = −0.61; p = 0.002) . Alrededor del 81% de los ninos fueron clasificados con NAFLD leve o moderada / severa, y estos grupos tenian un mayor consumo de HOMA-IR (p = 0.036) y de fructosa (p = 0.0014). Conclusiones: las ninas tuvieron mas alteraciones metabolicas. El grupo con niveles mas bajos de IGFBP-1 (IR hepatico) se asocio con un mayor IMC, HOMA-IR y consumo de fructosa; El grupo con mayor severidad de NAFLD mostro un mayor consumo de HOMA-IR y fructosa. EnglishBackground: Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective: The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods: A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results: We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions: The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption. (REV INVEST CLIN. 2019;71:339-48)

Infectious complications as a predictor of mortality in patients with non-hodgkin lymphoma receiving rituximab-containing chemotherapy

Abstract: espanolAntecedentes: el rituximab es un anticuerpo monoclonal que aumenta la supervivencia libre de enfermedad y la supervivencia general de pacientes con linfoma no Hodgkin (NHL) CD20 +. El objetivo de este estudio es describir la prevalencia y el espectro de infecciones en pacientes con LNH que reciben quimioterapia que contiene rituximab y el impacto en la supervivencia. Materiales y metodos: desde enero de 2011 hasta diciembre de 2012, se incluyeron todos los pacientes diagnosticados con LNH que recibieron al menos una dosis de rituximab. Resultados:Durante el periodo de estudio, 265 pacientes recibieron rituximab; 108 (40.8%) hombres; la edad media fue de 60 ± 15 anos. Hubo 177 infecciones en 85 pacientes, siendo la neutropenia febril mas comun (n = 38; 21.5%) y las infecciones relacionadas con la lesion de la barrera mucosa (n = 28; 15.8%). En 88 eventos (49%), hubo un diagnostico microbiologico, siendo la infeccion bacteriana la mas frecuente (39.6%), pero se desarrollo tuberculosis (TB) en 4 casos (1.5%; tasa de incidencia 721 / 100,000 persona-ano). Durante el seguimiento, 71 pacientes fallecieron (27%); en 35 casos, estuvo relacionado con la infeccion. No hubo diferencias en el seguimiento entre aquellos que murieron debido a una infeccion versus aquellos que murieron por otra causa (p = 0.188). El analisis multivariado de mortalidad mostro que la edad> 60 anos, el fracaso para lograr una respuesta completa, Conclusiones: es importante realizar una prueba de deteccion de TB en todos los pacientes que recibiran rituximab y mantener una monitorizacion constante para detectar un proceso infeccioso y comenzar el tratamiento lo antes posible. EnglishBackground: Rituximab is a monoclonal antibody that increases the disease-free and overall survival of patients with nonHodgkin lymphoma (NHL) CD20+. The objective of this study is to describe the prevalence and spectrum of infections in patients with NHL receiving rituximab-containing chemotherapy and the impact on survival. Materials and Methods: From January 2011 to December 2012, all patients diagnosed with NHL who received at least one dose of rituximab were included. Results: During the study period, 265 patients received rituximab; 108 (40.8%) males; the mean age was 60 ± 15 years. There were 177 infections in 85 patients, being the most common febrile neutropenia (n = 38; 21.5%) and mucosal barrier injury-related infections (n = 28; 15.8%). In 88 events (49%), there was a microbiologic diagnosis, being bacterial infection the most frequent (39.6%), but tuberculosis (TB) was developed in 4 cases (1.5%; incidence rate 721/100,000 person-year). During follow-up, 71 patients died (27%); in 35 cases, it was related to infection. There were no differences in follow-up between those who died due to infection versus those who died from another cause (p = 0.188). Multivariate analysis for mortality showed that age >60 years, failure to achieve a complete response, and development of an infectious complication increased the risk of death. Conclusions: It is important to perform a screening test for TB in all patients who will receive rituximab and maintain a constant monitoring to detect an infectious process and begin treatment as soon as possible. (REV INVEST CLIN. 2019;71:275-82)

Exploratory Analysis of Rare and Novel Variants in Mexican Patients Diagnosed with Schizophrenia and Dementia

Abstract: espanolAntecedentes: la esquizofrenia (SCZ) y la demencia, a menudo relacionadas, son dos de las enfermedades neuropsiquiatricas mas comunes; Los estudios epidemiologicos han demostrado que los pacientes con SCZ presentan un riesgo 2 veces mayor de demencia en comparacion con los individuos no esquizofrenicos. Exploramos la presencia de variantes geneticas daninas raras y novedosas en pacientes diagnosticados con demencia de inicio tardio de tipo Alzheimer (DAT) o SCZ. Metodos: Incluimos 7 pacientes con DAT y 12 con SCZ y realizamos una secuenciacion dirigida de gran profundidad de 184 genes. Resultados: Encontramos variantes daninas novedosas y raras en 18 genes en estos pacientes mexicanos. Los portadores de estas variantes mostraron fenotipos extremos, incluyendo SCZ resistente al tratamiento o deterioro cognitivo. Ademas, encontramos una variacion en ABCC1 como un posible vinculo entre la psicosis y el deterioro cognitivo. Discusion: Como analisis exploratorio, informamos algunas variaciones interesantes que deberian corroborarse en estudios de mayor tamano de muestra. EnglishBackground: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer’s type (DAT) or SCZ. Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies. (REV INVEST CLIN. 2019;71:246-54)

Factors influencing achievement of low-density lipoprotein cholesterol goals in mexico: the international cholesterol management practice study.

Abstract: espanolAntecedentes: el International Cholesterol Management Practice Study es un esfuerzo de colaboracion multinacional para describir la efectividad de la terapia de reduccion de lipidos (LLT), asi como las principales barreras para lograr los objetivos de colesterol de lipoproteinas de baja densidad (LDL-C) Objetivo: El objetivo del estudio fue investigar los factores asociados con el logro de las metas de LDL-C en Mexico utilizando datos de la vida real. Metodos: Este fue un estudio observacional transversal de 18 medicos de diferentes establecimientos de salud en Mexico, quienes brindaron informacion sobre sus practicas entre agosto de 2015 y agosto de 2016. Se incluyeron pacientes tratados durante ≥3 meses con cualquier LLT en los que la medicion de LDL-C en LLT estable estuvo disponible durante los 12 meses anteriores Resultados: se incluyeron 623 pacientes con una edad media de 59,3 ± 12,7 anos; El 55,6% eran mujeres. El valor medio de LDL-C en LLT fue 141,8 ± 56,1 mg / dL. En el momento de la inscripcion, el 97,4% de los pacientes estaban recibiendo tratamiento con estatinas (el 11,3% en tratamiento de alta intensidad). Solo el 24,8% de los pacientes con riesgo cardiovascular (CV) muy alto frente al 26,4% de los pacientes de alto riesgo y el 52,4% de los pacientes de riesgo moderado alcanzaron sus objetivos de c-LDL. Los factores independientes asociados con el incumplimiento del objetivo de LDL-C fueron intolerancia a las estatinas, sobrepeso y obesidad, obesidad abdominal, sexo femenino, alto riesgo CV, uso de servicios de salud publica, sindrome metabolico, diabetes tipo 2 e hipertrigliceridemia. Un mayor nivel de educacion se asocio con un menor riesgo de no lograr los objetivos de LDL-C Conclusiones: El logro de las metas de c-LDL es suboptimo en Mexico, especialmente en los pacientes con mayor riesgo CV. Las principales barreras para lograr el objetivo son facilmente detectables. La implementacion de LLT debe adaptarse a las necesidades y al perfil del paciente. EnglishBackground: The International Cholesterol Management Practice Study is a multinational collaborative effort to describe the effectiveness of the lipid-lowering therapy (LLT) as well as the main barriers to achieve the low-density lipoprotein cholesterol (LDL-C) goals. Objective: The objective of the study was to investigate factors associated with the achievement of LDL-C goals in Mexico using real-life data. Methods: This was a cross-sectional observational study from 18 physicians across different health facilities in Mexico, who provided information about their practices between August 2015 and August 2016. We in- cluded patients treated for ≥3 months with any LLT in whom LDL-C measurement on stable LLT was available for the previous 12 months. Results: We included 623 patients with a mean age of 59.3 ± 12.7 years; 55.6% were women. The mean LDL-C value on LLT was 141.8 ± 56.1 mg/dL. At enrollment, 97.4% of patients were receiving statin therapy (11.3% on high-inten- sity treatment). Only 24.8% of the very-high cardiovascular (CV) risk patients versus 26.4% of the high risk and 52.4% of the moderate risk patients achieved their LDL-C goals. Independent factors associated with non-achievement of LDL-C goal were statin intolerance, overweight and obesity, abdominal obesity, female sex, high CV risk, use of public health-care service, meta- bolic syndrome, type 2 diabetes, and hypertriglyceridemia. Higher-level of education was associated with a lower risk of not achieving LDL-C goals. Conclusions: Achievement of LDL-C goals is suboptimal in Mexico, especially in patients with the highest CV risk. The main barriers to achieve the goal are easily detectable. Implementation of LLT should be adapted to the patient’s needs and profile. (REV INVEST CLIN. 2019;71:408-16)

Bursectomy in gastric cancer surgery: a meta-analysis.

Abstract: espanolAntecedentes: la bursectomia consiste en extirpar quirurgicamente el revestimiento peritoneal que cubre el pancreas y el plano anterior del mesocolon transversal durante la gastrectomia. Sin embargo, hay pocos datos para indicar si la bursectomia tiene un beneficio clinico. Objetivo: El objetivo de este estudio fue estudiar el efecto de la bursectomia sobre las complicaciones, la recurrencia y la supervivencia general de los pacientes con cancer gastrico. Metodos: la literatura publica disponible desde enero de 2000 hasta julio de 2017 sobre la gastrectomia con bursectomia y la gastrectomia estandar para el cancer gastrico se recupero mediante busquedas en las bases de datos en linea nacionales e internacionales. El metanalisis se realizo despues del proceso de extraccion de datos. Resultados: finalmente se incluyeron ocho estudios para un total de 1644 pacientes, de los cuales 644 se sometieron a bursectomia y 1000 recibieron gastrectomia estandar sin bursectomia. Como se muestra en los resultados del metanalisis, no hubo diferencias estadisticamente significativas en la presencia de complicaciones postoperatorias totales (odds ratio [OR] = 1.06, intervalo de confianza [IC] del 95% [0.83-1.35], p = 0.63) , recurrencia general (OR = 1.07, IC 95% [0.77-1.50], p = 0.68), supervivencia general a 3 anos (OR = 1.30, IC 95% [0.82-2.07], p = 0.26) y 5 anos supervivencia global (OR = 0,91; IC del 95% [0,66-1,27], p = 0,58). Conclusion: aunque la aplicacion de la bursectomia en la gastrectomia radical no aumento las complicaciones postoperatorias, no ofrecio ningun beneficio para controlar la recurrencia del tumor o mejorar la supervivencia general. EnglishBackground: Bursectomy consists of surgically removing the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon during gastrectomy. However, there are little data to indicate whether bursectomy has a clinical benefit. Objective: The objective of this study was to study the effect of bursectomy on complications, recurrence, and overall survival of patients with gastric cancer. Methods: The publicly available literature published from January 2000 to July 2017 concerning gastrectomy with bursectomy and standard gastrectomy for gastric cancer was retrieved by searching the national and international online databases. Meta-analysis was performed after the data extraction process. Results: Eight studies were finally included for a total of 1644 patients, of whom 644 underwent bursectomy and 1000 received standard gastrectomy without bursectomy. As shown by the meta-analysis results, there were no statistically significant differences in the presence of total post-operative complications (odds ratio [OR] = 1.06, 95% confidence interval [CI] [0.83-1.35], p = 0.63), overall recurrence (OR = 1.07, 95% CI [0.77-1.50], p = 0.68), 3-year overall survival (OR = 1.30, 95% CI [0.82-2.07], p = 0.26), and 5-year overall survival (OR = 0.91, 95% CI [0.66-1.27], p = 0.58). Conclusion: Although application of bursectomy in radical gastrectomy did not increase post-operative complications, it offered no benefit to control tumor recurrence or improve overall survival. (REV INVEST CLIN. 2019;71:98-105)

Evaluation of the royal free hospital cirrhosis glomerular filtration rate formula in hispanic patients with cirrhosis: an external validation.

Abstract: espanolAntecedentes y objetivos: La medicion de la tasa de filtracion glomerular (TFG) en pacientes con cirrosis hepatica (LC) es el metodo ideal para una evaluacion adecuada de la funcion renal. Sin embargo, es invasivo, costoso y poco accesible. Ademas, la estimacion de la TFG en pacientes con cirrosis ha sido inexacta. El objetivo del presente estudio fue evaluar y validar la formula del Royal Free Hospital (RFH) recientemente descrita en una cohorte hispana de pacientes con LC y compararla con otras formulas, incluida la ecuacion CKD-EPI cystatin C. Metodos: se midio la TFG a traves del aclaramiento renal de Tc-99m DTPA; se evaluo de forma transversal y se comparo con los TFG que se estimaron utilizando las siguientes formulas: RFH, Cockcroft-Gault, Modificacion de la dieta con 6 variables en la enfermedad renal-6, CKD-EPI cistatina C, CKD-EPI Creatinina y CKD- EPI Cystatin C-Creatinine. Resultados: Se incluyeron 76 pacientes (53% mujeres). La TFG media medida en toda la cohorte fue de 64 ml / min / 1,73 m2; El 54% de los pacientes tenian una TFG Conclusiones: La formula RFH mostro un mejor desempeno que las otras formulas basadas en creatinina serica en una poblacion hispana con LC. No hubo diferencia en el rendimiento entre la formula RFH y la formula CKD-EPI cistatina C. espanol. EnglishBackground and Aims: Glomerular filtration rate (GFR) measurement in patients with liver cirrhosis (LC) is the ideal method for adequate evaluation of kidney function. However, it is invasive, costly, and not widely accessible. Moreover, GFR estimation in patients with cirrhosis has been inaccurate. The aim of the present study was to evaluate and validate the recently described Royal Free Hospital (RFH) formula in a Hispanic cohort of patients with LC and compare it with other formulas, including the CKD-EPI cystatin C equation. Methods: GFR was measured through the renal clearance of Tc-99m DTPA; it was cross-sectionally evaluated and compared with GFRs that were estimated utilizing the following formulas: RFH, Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease-6, CKD-EPI cystatin C, CKD-EPI Creatinine, and CKD-EPI Cystatin C-Creatinine. Results: We included 76 patients (53% women). The mean measured GFR in the entire cohort was 64 ml/min/1.73m2; 54% of the patients had a GFR

Could neutrophil extracellular traps be the new prognostic markers of cancer

Abstract: espanolLas trampas extracelulares de neutrofilos (NET) se describieron hace mas de una decada, pero recientemente, el interes en estas estructuras ha aumentado debido a su participacion en la progresion del cancer, la trombosis relacionada con el cancer y el desarrollo de metastasis. Este papel protumoral de los NET fortalece su potencial como nuevos marcadores pronosticos de cancer. EnglishNeutrophil extracellular traps (NETs) were described more than one decade ago, but recently, the interest in these structures has increased due to their involvement in cancer progression, cancer-related thrombosis, and development of metastasis. This protumoral role of NETs strengthens their potential as new prognostic markers of cancer. (REV INVEST CLIN. 2019;71:365-8)

Factors predicting the stretching exercise behaviors of office employees working in the shahid beheshti university of medical sciences in tehran, iran.

Abstract: espanolAntecedentes: los empleados de oficina de todas las edades corren el riesgo de contraer enfermedades no transmisibles, como los trastornos musculoesqueleticos (TME) debido a la inactividad fisica. El comportamiento del ejercicio de estiramiento (SE) podria ayudar a los empleados de oficina a prevenir los TME. Esta investigacion tuvo como objetivo estudiar los predictores de SE entre los empleados de oficina que trabajan en la Universidad de Ciencias Medicas Shahid Beheshti (SBUMS) de Iran a traves de un modelo de promocion de la salud (HPM). Metodos: en el presente estudio, 430 empleados de oficina elegibles fueron seleccionados al azar. Para evaluar los predictores de SE, todos los constructos de HPM se examinaron como factores de riesgo para determinar si influyen en la probabilidad de ocurrencia de comportamiento de SE y se interpretaron a traves de odds ratio (OR). SPSS version 19 se utilizo para analizar los datos. Resultados: un total de 420 empleados de oficina con una edad media de 37,1 ± 8,03 anos participaron en el estudio. Este estudio demostro que las barreras percibidas para la accion podrian evitar que los participantes se involucren en SE (OR [IC 95%]: 0.875 [0.815-0.939], p Conclusiones: Este estudio mostro que los empleados de la oficina que tenian mas confianza y estaban comprometidos con un plan de accion, y percibian menos barreras, tenian mas probabilidades de participar en el comportamiento de SE. EnglishBackground: Office employees of all ages are at risk for non-communicable diseases such as musculoskeletal disorders (MSDs) due to physical inactivity. Stretching exercise (SE) behavior could help office employees prevent MSDs. This research aimed to study the predictors of SE among office employees working in Shahid Beheshti University of Medical Sciences (SBUMS) of Iran through a health promotion model (HPM). Methods: In the present study, 430 eligible office employees were randomly selected. To assess the predictors of SE, all the HPM constructs were examined as risk factors to determine whether they influence the probability of SE behavior occurrence and were interpreted through odds ratio (OR). SPSS version 19 was used to analyze the data. Results: A total of 420 office employees with mean age of 37.1 ± 8.03 years took part in the study. This study showed that perceived barriers to action could prevent participants from engaging in SE (OR [95% CI]: 0.875 [0.815-0.939], p 2019;71:178-85)

Left atrial function and volume by magnetic resonance in patients with hereditary amyloidosis.

Abstract: espanolAntecedentes: el agrandamiento de la auricula izquierda (AI) es un predictor confiable de eventos cardiovasculares adversos, y la funcion auricular reducida es un factor de riesgo independiente de mortalidad en pacientes con amiloidosis. El objetivo de este estudio fue caracterizar la funcion de la AI en pacientes mexicanos con diagnostico confirmado de amiloidosis transtiretina hereditaria (transtiretina amiloide [ATTR]). Metodos: Se incluyeron en el estudio todos los pacientes consecutivos con diagnostico de ATTR hereditario que se sometieron a un estudio de resonancia magnetica cardiaca en el periodo de marzo de 2016 a junio de 2017; Se evaluaron los volumenes y la funcion de la auricula izquierda. Resultados: los pacientes se dividieron en dos grupos, uno con amiloidosis cardiaca y otro sin ella. Se observaron diferencias estadisticamente significativas entre ambos grupos en terminos de volumen de AI maximo indexado, 26 ml versus 35,9 ml, p = 0,03; volumen de AI minimo indexado, 10,7 ml frente a 13,6 ml, p = 0,03; y volumen de precontraccion de AI indexado, 17 mL versus 22,4 mL, p = 0,03. No se observaron diferencias estadisticamente significativas entre ambos grupos al comparar ni los diferentes volumenes de eyeccion ni las diferentes fracciones de eyeccion Conclusiones: Los pacientes con ATTR hereditaria con afectacion cardiaca presentan remodelado de la auricula izquierda, con aumento de los volumenes auriculares, sin disminuir su funcion. EnglishBackground: Left atrial (LA) enlargement is a reliable predictor of adverse cardiovascular events, and reduced atrial function is an independent risk factor for mortality in patients with amyloidosis. The objective of this study was to characterize the LA function in Mexican patients with a confirmed diagnosis of hereditary transthyretin amyloidosis (amyloid transthyretin [ATTR]). Methods: All consecutive patients with diagnosis of hereditary ATTR who underwent a cardiac magnetic resonance study in the period from March 2016 to June 2017 were included in the study; the volumes and function of the left atrium were evalu- ated. Results: Patients were divided into two groups, one with and one without cardiac amyloidosis. Statistically significant differences were observed between both groups in terms of indexed maximal LA volume, 26 mL versus 35.9mL, p = 0.03; indexed minimal LA volume, 10.7 mL versus 13.6mL, p = 0.03; and indexed LA pre-contraction volume, 17 mL versus 22.4mL, p = 0.03. No statistically significant differences were observed between both groups when comparing neither different ejection volumes nor the different ejection fractions. Conclusions: Patients with hereditary ATTR with cardiac involvement have remodeling of the left atrium, with increased atrial volumes, without diminishing its function. (REV INVEST CLIN. 2019;71:387-92)