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BACKGROUND: Nodularity in thyroid tissue is extremely common. In Mexico, the only openly available treatment for benign cold thyroid nodules that cause compressive or cosmetic symptoms is surgery. This limitation in the availability of non-invasive treatments places an enormous strain on the State's health resources. OBJECTIVE: To demonstrate the cost-minimization of percutaneous ethanol injection treatment (PEIT) against radiofrequency ablation (RFA) and laser ablation for the treatment of benign solid thyroid nodules. METHOD: Prospective, comparative, quasi-experimental, longitudinal study with external controls, non-randomized, historical, prolective and open. The significant difference in volume reduction was calculated by paired 2-tailed t-test. Validation was made to prove that the reduction in the final nodule volume was non-inferior to the gold standard. The cost-analysis study was carried out using the Montecarlo method. RESULTS: 15 patients entered the study. The mean volume of the nodules was 14.46 ± 19 cc, with a final mean volume of 5.24 ± 8.44 cc, the average reduction percentage was 63 ± 17%. The cost per procedure was $ 18,807 mx, $ 16,300 mx, $ 9,248 mx and $ 1,615 for RFA, surgery, laser ablation and PEIT, respectively. CONCLUSIONS: The results of the study demonstrate the non-inferiority of the ablation of benign solid thyroid nodules with PEIT compared to laser and RFA, at a lower cost.

ANTECEDENTES: La nodularidad en el tejido tiroideo es extremadamente común. En México, el único tratamiento disponible abiertamente para los nódulos tiroideos fríos benignos que causan síntomas compresivos o estéticos es la cirugía. Esta limitante en la disponibilidad de tratamientos no invasivos pone una enorme demanda sobre los recursos de salud del Estado. OBJETIVO: Demostrar el costo-minimización del tratamiento por inyección percutánea con etanol (PEIT, percutaneous etanol injection treatment) contra la ablación por radiofrecuencia (RFA, radiofrequency ablation) y el rayo láser para el tratamiento de nódulos tiroideos sólidos benignos. MÉTODO: Estudio prospectivo, comparativo, cuasiexperimental, longitudinal, con controles externos, no aleatorizado, histórico, prolectivo y abierto. La diferencia significativa en la reducción de volumen se calculó mediante prueba t pareada a dos colas. Se validó que el porcentaje de reducción en el volumen final fue tan eficiente como el método de referencia. El estudio de análisis de costos se realizó utilizando el método de Montecarlo. RESULTADOS: Ingresaron al estudio 15 pacientes. El volumen medio de los nódulos fue de 14.46 ± 19 cc, con un volumen medio final de 5.24 ± 8.44 cc. El porcentaje de reducción medio fue del 63 ± 17%. El costo por procedimiento fue de $18,807 mx para la RFA, $16,300 mx para la cirugía, $9248 mx para la ablación láser y $1615 mx para el PEIT. CONCLUSIONES: Los resultados del estudio demuestran la no inferioridad de la ablación de nódulos tiroideos sólidos benignos con PEIT en comparación con el rayo láser y la RFA, a un costo inferior.

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Resumen Introducción: El cáncer de próstata es la principal causa de muerte por cáncer en México, el diagnóstico inicial se hace mediante la medición del antígeno prostático específico y el tacto rectal de la próstata. Sin embargo, hay limitaciones que incluye la capacidad para distinguir con precisión los pacientes con y sin cáncer y aquellos que presentan una forma agresiva de la enfermedad. Los microRNAs se encuentran alterados en el tejido prostático canceroso, incluyendo aquellos casos fármaco resistentes. Los miRNAs son reguladores de la expresión génica y se encuentran involucrados en diversos procesos patológicos. Se ha demostrado que estas moléculas son detectables en orina. Objetivo: Esta revisión presenta la información sobre cuáles son los miRNAs reportados en orina como posibles marcadores para el diagnóstico, pronóstico y respuesta a la terapia en cáncer de próstata. Resultados: De la búsqueda realizada en la bibliografía, se encontraron 13 miRNAs en los diferentes estudios, miR-19a, miR-19b, miR-21, miR-148a, miR-375, miR-125b-5p, miR-151-5p, miR-141, miR-200b, miR-221, miR-107, miR-26b-5p, miR-205-5p. Teniendo algunos miRNAs como miR-375, miR-21, miR-141 encontrados en varios estudios. Limitaciones del estudio o implicaciones: Se puede concluir es factible obtener la medición por métodos no invasivos de miRNAs en pacientes con cáncer de próstata. Originalidad o valor: Es un estudio de revisión respecto a los miRNAs obtenidos en muestras de orina en pacientes con cáncer de próstata.

Abstract Introduction: Prostate cancer is the leading cause of cancer death in Mexico, the initial diagnosis is made by measuring the Prostate Specific Antigen and the digital rectal examination of the prostate. However, there are limitations including the ability to accurately distinguish patients with and without cancer and those with an aggressive form of the disease. MicroRNAs are altered in cancerous prostate tissue, including drug-resistant cases. MiRNAs are regulators of gene expression and are involved in various pathological processes. These molecules have been shown to be detectable in urine. Objective: This review presents the information on which are the miRNAs reported in urine as possible markers for the diagnosis, prognosis and response to therapy in prostate cancer. Results: From the literature search, 13 miRNAs were found in the different studies, miR-19a, miR-19b, miR-21, miR-148a, miR-375, miR-125b-5p, miR-151-5p , miR-141, miR-200b, miR-221, miR-107, miR-26b-5p, miR-205-5p. Having some miRNAs like miR-375, miR-21, miR-141 found in various studies. Limitations of the study or implications: It can be concluded that it is feasible to obtain the measurement of miRNAs by non-invasive methods in patients with prostate cancer. Originality or value: It is a review study regarding miRNAs obtained in urine samples in patients with prostate cancer.

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We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

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INTRODUCTION: Fundus autofluorescence (FAF) has shown sensitivity in the detection of macular edema. OBJECTIVES: To evaluate indices formed with FAF and retinal anatomical-functional variables in patients with diabetic macular edema (DME) treated with ziv-aflibercept (ziv-AFL). METHODS: Twenty-nine eyes of 15 DME patients who received ziv-AFL intravitreal injections were included in the study. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT) and FAF were evaluated before treatment and at one and two months. OCT variables were central subfield thickness (CST), macular volume (MV) and macular cube average thickness (MCAT). FAF/BCVA, FAF/CS, FAF/CST, FAF/MV and AF/MCAT indices baseline values were obtained. Analysis was performed with Spearman's rank correlation coefficient and linear regression analysis. RESULTS: There was a significant correlation between baseline FAF/BCVA index and BCVA at second month (rs = - 0.78, p = 0.000), between baseline FAF/CS index and BCVA at second month (rs = -0.68, p = 0.0009) and between baseline FAF/CS index and MV at first month of follow-up (rs = 0.64, p = 0.002). CONCLUSIONS: In DME, composite indices with baseline FAF predict variables such as BCVA in the follow-up of patients receiving ziv-AFL.

INTRODUCCIÓN: La autofluorescencia retiniana (AF) ha mostrado sensibilidad en la detección del edema macular. OBJETIVOS: Evaluar índices formados con la AF y variables anatomofuncionales retinianas en pacientes con edema macular diabético (EMD) tratados con ziv-aflibercept (ziv-AFL). MÉTODOS: Fueron incluidos 29 ojos de 15 pacientes con EMD que recibieron inyecciones intravítreas de ziv-AFL. Se evaluó agudeza visual mejor corregida (AVMC), sensibilidad al contraste (SC), tomografía de coherencia óptica (TCO) y AF, antes del tratamiento, así como al primer y segundo mes de iniciado este. Las variables de la TCO fueron grosor foveal central (GFC), volumen macular (VM) y grosor promedio macular (GPM). Se obtuvieron los valores basales de AF/AVMC, AF/SC, AF/GFC, AF/VM y AF/GPM. Se realizó análisis con el coeficiente de correlación de rangos de Spearman y análisis de regresión lineal. RESULTADOS: Hubo una correlación significativa entre el índice AF/AVMC basal y la AVMC en el segundo mes (rs = −0.78, p = 0.000), entre el índice AF/SC basal y la AVMC en el segundo mes (rs = −0.68, p = 0.0009) y entre AF/SC basal y el VM en el primer mes de seguimiento (rs = 0.64, p = 0.002). CONCLUSIONES: En el EMD, los índices compuestos con AF basales predicen variables como AVMC en el seguimiento de pacientes que reciben ziv-AFL.

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PURPOSE: To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose. METHODS: Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman's rank correlation coefficient, linear regression, and interobserver-agreement analysis. RESULTS: There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept (rs = -0.78, p = .000 and rs = -0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up (rs = 0.56, p = .008 and (rs = 0.64, p = .002, respectively). CONCLUSION: This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.

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BACKGROUND AND OBJECTIVE: The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. METHODS: This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact® infusion. RESULTS: Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery - 52.5% of the cases, gynecology/obstetrics - 17.5%, general surgery and orthopedics - 12.5% each, and hematology and neurosurgery - 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. CONCLUSIONS: In this real-life post-marketing study, the safety profile of Clottafact® was very similar to previous reports. Thus, Clottafact® shows a favorable safety profile in clinical practice.

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INTRODUCTION: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. OBJECTIVE: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. METHOD: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. RESULTS: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), focal hyper-autofluorescent (17%), multi-focal hyper-autofluorescent (22%) and plaque-like hyper-autofluorescent (8%). The kappa coefficient was 0.906 (p = 0.000). CONCLUSIONS: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

INTRODUCCIÓN: Los pacientes con edema macular diabético pueden presentar alteraciones en la autofluorescencia retiniana, que hasta el momento han sido analizadas más con sistemas de láser de barrido o confocales. OBJETIVO: Describir y clasificar los patrones anormales de autofluorescencia retiniana en pacientes con edema macular diabético mediante el sistema de autofluorescencia retiniana con cámara de flash. MÉTODO: Estudio observacional, retrospectivo, transversal y descriptivo. Se evaluaron imágenes digitales de autofluorescencia retiniana de casos no comparativos con edema macular diabético no tratado, obtenidas y almacenadas con el sistema de cámara de flash.Se evaluó la variabilidad interobservador. RESULTADOS: Se incluyeron 37 ojos de 20 pacientes. La opacidad de medios fue la causa más común de calidad inadecuada de imagen. Se observaron cinco diferentes patrones de autofluorescencia retiniana: disminuida (13 %), normal (40 %), hiperautofluorescente unifocal (17 %), hiperautofluorescente multifocal (22 %) e hiperautofluorescente en placa (8 %). El coeficiente kappa fue de 0.906 (p = 0.000). CONCLUSIONES: En pacientes con edema macular diabético se presentan diferentes patrones fenotípicos de autofluorescencia retiniana con los sistemas de cámara de flash. Una clasificación fenotípica más precisa pudiera ayudar a establecer factores pronósticos de pérdida visual o al diseño de ensayos clínicos relativos a edema macular diabético.

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Introduction: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. Objective: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. Method: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. Results: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), single-spot hyper-autofluorescent (17 %), multiple-spot hyper-autofluorescent (22 %) and plaque-like hyper-autofluorescent (8 %). The kappa coefficient was 0.906 (p = 0.000). Conclusions: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

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BACKGROUND: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. METHODS: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. RESULTS: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G>T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. CONCLUSIONS: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.

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