Precisión y fiabilidad de la medición del índice tobillo-brazo utilizando un dispositivo oscilométrico versus el método Doppler / Accuracy and reliability of ankle-brachial index measurement using an oscillometric device versus the Doppler method

Introducción: la medición del índice tobillo-brazo (ITB) es una prueba de primera línea y con alta precisión diagnóstica para detectar la enfermedad vascular periférica (EVP). El método Doppler, considerado el estándar de oro, requiere del dispositivo y de un operador capacitado, lo que limita su uso en la atención primaria. Como alternativa, un método oscilométrico que emplea un dispositivo de presión arterial automático es una prueba simple y accesible que podría minimizar los sesgos del observador y eliminar la necesidad de capacitación especial. Objetivos: validar la capacidad diagnóstica de un dispositivo oscilométrico automatizado frente al método Doppler para la medición del ITB. Materiales y métodos: se incluyeron pacientes con diabetes mellitus tipo 1 y 2 (DM1 y DM2), mayores de 50 años, con uno o más factores de riesgo cardiovascular. Luego de que los pacientes permanecieran 5 minutos acostados, se registró la presión arterial sistólica (PAS) con tensiómetro Welch Allyn DS 45-11 y Doppler Vascular Contec Sonoline B 8 Mhz en ambas arterias tibiales posteriores y en arteria braquial derecha. Posteriormente se realizaron los mismos registros con monitor de presión arterial automático modelo Omrom HEM-7130. Se calculó el ITB de cada miembro inferior y las capacidades diagnósticas (sensibilidad [S-, especificidad [E], concordancia por coeficiente kappa, valor predictivo positivo [VPP] y valor predictivo negativo [VPN]) del método oscilométrico para detectar un ITB patológico por Doppler (≤0,90). Resultados: se evaluaron 66 pacientes, 52 varones y 14 mujeres, 7 con DM1 y 59 con DM2, 69 años de edad (DS 9,8), con una antigüedad de la DM de 18,05 años (DS 12,01). La prevalencia de EVP detectada por Doppler (ITB ≤0,90) fue del 16,7% (IC 95% 9,9-23,4). El método oscilométrico para detectar un ITB ≤0,90 por Doppler mostró una S del 72,7% (IC 95% 51,8-93,6), una E del 96,3% (IC 95% 92,4-100), una concordancia del 92,4% (IC 95% 87,5-97,3), un VPP del 80,0% (IC 95% 59,9-100) y un VPN del 94,6% (IC 95% 90,0-99,3). Conclusiones: el alto VPN hallado (condición esencial para un método de screening) significa que si el método oscilométrico da un ITB >0,90, hay un 94,6% de posibilidad de que el ITB por Doppler no sea ≤0,90. El VPP de 80% encontrado significa que si el ITB oscilométrico es ≤0,90, hay un 80% de posibilidad de que el ITB Doppler sea verdaderamente ≤0,90. Por lo tanto, consideramos que la simple medición del ITB con el método oscilométrico podría recomendarse en la atención primaria, donde se requieren métodos rápidos, fáciles y confiables.

Introduction: the measurement of the ankle-brachial index (ABI) is a first-line test with high diagnostic accuracy for the detection of peripheral vascular disease. The Doppler method, considered the gold standard, requires the device and a trained operator, which limits its use in primary care. Alternatively, an oscillometric method using an automated blood pressure device is a simple and affordable test that could minimize observer bias and eliminate the need for special training. Objectives: to validate the diagnostic capacity of an automated oscillometric device against the Doppler method for ABI measurement. Materials and methods: diabetes mellitus type 1 and 2 (DM1 and DM2) patients older than 50 years with 1 or more cardiovascular risk factors were included. After 5 minutes lying down, SBP was recorded with a Welch Allyn DS 45-11 sphygmomanometer and Contec Sonoline B 8 Mhz Vascular Doppler in both posterior tibial arteries and in the right brachial artery. Subsequently, the same recordings were made with an Automatic Blood Pressure Monitor Model Omrom HEM-7130. The ABI of each lower limb and the diagnostic capabilities (sensitivity [S], specificity [E], concordance by kappa coefficient, positive predictive value [PPV] and negative predictive value [NPV] of the oscillometric method to detect a pathological ABI were calculated by Doppler (≤0.90). Results: 66 patients were evaluated, 52 men and 14 women, 7 DM1 and 59 DM2, 69 years old (SD 9.8) with a history of diabetes of 18.05 years (SD 12.01). The prevalence of PVD detected by Doppler (ABI ≤0.90) was 16.7% (95% CI 9.9-23.4). The oscillometric method to detect an ABI ≤0.90 by Doppler showed an S of 72.7% (95% CI 51.8-93.6), an E of 96.3% (95% CI 92.4-100), a concordance of 92.4% (95% CI 87.597.3), a PPV of 80.0% (95% CI 59.9-100) and a NPV of 94.6% (95% CI 90 .0-99.3). Conclusions: the high NPV found (essential condition for a screening method) means that if the oscillometric method gives an ABI >0.90, there is a 94.6% chance that the Doppler ABI is not ≤0.90. The PPV of 80% found means that if the oscillometric ABI is ≤0.90, there is an 80% chance that the Doppler ABI is truly ≤0.90. Therefore, we consider that the simple measurement of ABI with the oscillometric method could be recommended in primary care, where fast, easy and reliable methods are adequate.

Stability-indicative and conformation-specific enzyme linked immunosorbent assay for analysis of recombinant human gamma interferon.

Recombinant human interferon gamma (rhIFN-γ) is a promising molecule for the treatment of several diseases. A pair of conformation-specific monoclonal antibodies (mAbs) against rhIFN-γ was selected from generated hybridoma cell lines to design a sensitive, stability-indicative, sandwich-type ELISA. The main assay parameters were optimized by the checkerboard method for the highest signal-to-noise ratio: assay buffer composition, coating buffer pH and composition, coating temperature-incubation time parameters, and coating mAb concentration and conjugate dilution. Detection and quantification limits were estimated between 0.019 and 0.078 ng/mL, respectively, and recovery values were from 92.03% to 98.40%. The coefficient of variation of intra-assay precision parameters ranged from 2.32% to 9.21% while the inter-analyst variation was between 4.70% and 10.63%, supporting the method's repeatability. The ELISA was specific for correctly folded and non-aggregated molecular species, as compared to intrinsic Trp fluorescence (chemical denaturation) and optical density at 340 nm (thermal aggregation), respectively. However, the method was not sensitive to the small C-terminal degradation of full-length rhIFN-γ1-144 (losses of 6-12 amino acid residues) as compared to results with mass spectrometry and gel electrophoresis. ELISA showed good correlation with rhIFN-γ antiviral biological activity. This method was applied to the stability evaluation of rhIFN-γ in physiological buffer at low concentrations using polypropylene and glass vials also in the presence of adsorption protectant excipients. Furthermore, ELISA could be adapted to other applications such as quantification of IFN-γ in serum samples, Mycobacterium tuberculosis diagnosis, etc.

Dispositivos cardíacos implantables y uso de resonancia magnética / Cardiac implantable devices and use of magnetic resonance / Dispositivos cardíacos implantáveis e utilização da ressonância magnética

El uso de la resonancia magnética (RM) en las distintas áreas de la medicina se ha expandido de manera significativa y de forma diaria se solicitan numerosos estudios. El hecho de que los resonadores pueden interaccionar con algunos objetos ha llevado a que históricamente se les niegue la realización de este estudio a pacientes portadores de dispositivos cardíacos porque se entiende que existen contraindicaciones absolutas. El avance de la tecnología de los dispositivos y la creciente evidencia publicada han cambiado este concepto. Nos proponemos revisar los mecanismos por los cuales un dispositivo implantable puede interactuar con el resonador y las implicancias clínicas que esto podría tener si las hubiera. La mayoría de los pacientes portadores de dispositivos cardíacos de estimulación podrán realizarse una RM, pero para que este procedimiento sea seguro es importante conocer las características y el tipo específico de dispositivo implantado. Proponemos finalmente puntos clave y algoritmos para tener en cuenta para el manejo adecuado de estos pacientes.

The use of magnetic resonance imaging (MRI) in different areas of medicine has expanded significantly and numerous procedures are indicated daily. The fact that resonators could interact with some objects has historically led to patients with cardiac devices being denied an MRI on the understanding that they suppose an absolute contraindication. Advances in device technology and the increasing evidence have changed this concept. We intend to review the mechanisms by which an implantable device could interact with the resonator and the clinical implications that this could have if any. Most patients will be able to undergo these studies, but to determine the safety of performing an MRI it is important to know the characteristics and specific type of implanted device. Finally, we provide key points and algorithms to take into account for these patients.

O uso da ressonância magnética em diferentes áreas da medicina tem se expandido significativamente e inúmeros exames são indicados diariamente. A possibilidade de que os ressonadores interajam com alguns objetos historicamente levou os pacientes com dispositivos cardíacos a terem a ressonância magnética negada por entender que existem contraindicações absolutas. Os avanços na tecnologia de dispositivos e o aumento das evidências publicadas mudaram esse conceito. Pretendemos revisar os mecanismos pelos quais um dispositivo implantável pode interagir com o ressonador e as implicações clínicas que isso pode ter, se houver. A grande maioria dos pacientes poderá se submeter a esses estudos, mas para determinar a segurança de realizar uma ressonância magnética é importante conhecer as características e o tipo específico de dispositivo implantado. Por fim, propomos pontos e algoritmos para a gestão dos pacientes.

Cumplimiento de objetivos en pacientes adultos con diabetes mellitus tipo 1: tasa estimada de disposición de glucosa como marcador clínico / Achievement of objectives in adult patients with type 1 diabetes mellitus: estimated glucose disposition rate as a clinical marker

Resumen Introducción: las guías de práctica clínica en diabetes mellitus (DM) establecen objetivos clínicos precisos sobre el buen manejo de la enfermedad, pero poco se sabe sobre el adecuado cumplimiento en nuestro medio. El sobrepeso y el sedentarismo han generado estigmas de síndrome metabólico en la población con DM1. Objetivos: evaluar el cumplimiento en cinco de dichos criterios: HbA1c <7%, c-LDL ≤100 mg/dl, actividad física ≥3 veces/ semana, tensión arterial sistólica (TAS) <140 mm Hg y no tabaquismo, y su asociación con insulinorresistencia determinada por la tasa estimada de disposición de glucosa (TeDG). Materiales y métodos: en 415 DM1 ≥18 años, 52% mujer y una edad de 34,8±13,9 años, se evaluó HbA1c, c-LDL, frecuencia semanal de actividad física (AF) estructurada, TAS y tabaquismo actual. Se determinó el grado de asociación a género, edad, antigüedad de la DM, nivel de educación, cobertura médica, índice de masa corporal (IMC) y sensibilidad a la insulina medida a través de la TeDG. Las variables cualitativas se analizaron por test de chi. y las cuantitativas por test de ANOVA I con post hoc por test de Tukey. Un valor de p<0,05 se consideró estadísticamente significativo. En todos los casos se utilizó un intervalo de confianza del 95%. Resultados: el 94,8% presentó TAS <140 mm Hg, el 82,2% no tabaquismo actual, el 56,5% c-LDL ≤100 mg/dL, el 39% AF ≥3 veces/semana y el 20,3% HbA1c <7%. Solo 26 pacientes (6,2%) alcanzaron en forma combinada los cinco objetivos analizados. El cumplimiento de dichos objetivos se asoció a nivel de educación secundaria o mayor (p=0,002) y cobertura de salud con obra social o prepaga (p=0,002). Hubo asociación significativa entre la TeDG en quienes cumplieron los cinco objetivos (p=0,02) y en forma individual en cuatro de ellos (TAS, c-LDL, HbA1c y AF). Conclusiones: de los 415 pacientes evaluados, el 6,2% cumplió los cinco objetivos. Solo el control de la TAS, no fumar y un c-LDL <100 mg/dL lo cumplió la mayoría de los pacientes. Una HbA1c <7% fue el objetivo individual que presentó menor grado de cumplimiento.

Abstract Introduction: the clinical practice guidelines in diabetes mellitus (DM) establish precise clinical objectives for the good management of the disease, but little is known about adequate compliance in our environment. Being overweight and sedentary have generated stigmas of metabolic syndrome in the population with DM1. Objectives: to evaluate the compliance with 5 of these criteria: HbA1c <7%, c-LDL ≤100 mg/dL, physical activity (PA) ≥3 times/week, systolic blood preasure (SBP) <140 mm Hg, and no smoking and its association with insulin resistance determined by the estimated glucose disposition rate (eGDR). Materials and methods: in 415 DM1 ≥18 years, 52% women, age 34.8±13.9 years, HbA1c, c-LDL, weekly frequency of structured PA, SBP, and current smoking were evaluated. The degree of association with gender, age, age of DM, level of education, medical coverage, BMI, and insulin sensitivity measured through eGDR was determined. Qualitative variables were analyzed by chi-square test and quantitative variables by ANOVA I test and analysis post hoc by Tukey's test for multiple comparisons. A value of p<0.05 was considered statistically significant. A 95% confidence interval was used in all cases. Results: systolic BP <140 mm Hg presented 94.8%, current non-smoking 82.2%, c-LDL ≤ 100 mg/dL 56.5%, physical activity (PA) ≥3 times a week 39% and HbA1c <7% 20.3%. Only 26 patients (6.2%) achieved the 5 objectives analyzed in combination. The fulfillment of the 5 objectives was associated at the level of ≥ secondary education (p=0.002) and health coverage with social welfare or prepaid (p=0.002). There was a significant association between TeDG in those who fulfilled the 5 objectives (p=0.02) and individually in 4 of them (SPB, c-LDL, HbA1c, and PA). Conclusions: of the 415 patients evaluated in our study, only 6.2% met the 5 criteria under consideration. Only control of SBP, non-smoking and c-LDL <100 were complied with by the majority of the patients. HbA1c <7% was the individual objective with the lowest degree of compliance.

Distribution of human papillomavirus genotypes by severity of cervical lesions in HPV screened positive women from the ESTAMPA study in Latin America.

The proportion of HPV16 and 18-associated cervical cancer (CC) appears rather constant worldwide (≥70%), but the relative importance of the other HR-HPV differs slightly by geographical region. Here, we studied the HPV genotype distribution of HPV positive Latin American (LA) women by histological grade, in a sub-cohort from the ESTAMPA study; we also explored the association of age-specific HPV genotypes in severe lesions. Cervical samples from 1,252 participants (854 ≤CIN1, 121 CIN2, 194 CIN3 and 83 CC) were genotyped by two PCRs-Reverse Blotting Hybridization strategies: i) Broad-Spectrum General Primers 5+/6+ and ii) PGMY9/11 PCRs. HPV16 was the most frequently found genotype in all histological grades, and increased with the severity of lesions from 14.5% in ≤ CIN1, 19.8% in CIN2, 51.5% in CIN3 to 65.1% in CC (p < 0.001). For the remaining HR-HPVs their frequency in CC did not increase when compared to less severe categories. The nonavalent vaccine HR-types ranked at the top in CC, the dominant ones being HPV16 and HPV45. HR-HPV single infection occurs, respectively, in 57.1% and 57.0% of ≤CIN1 and CIN2, increasing to 72.2% and 91.6% in CIN3 and CC (p<0.001). No association between age and HPV type was observed in CC, although the risk of HPV16 infection in CIN3 cases increased with age. Results confirm the relevance of HPV16 in the whole clinical spectrum, with a strong rise of its proportion in CIN3 and cancer. This information will be relevant in evaluating the impact of HPV vaccination, as a baseline against which to compare genotype changes in HPV type-specific distribution as vaccinated women participate in screening in LA region. Likewise, these data may help select the best HPV testing system for HPV-based efficient, affordable, and sustainable screening programmes.

GeneXpert como método de diagnóstico de la tuberculosis en Santiago de Cuba / GeneXpert as diagnostic method of tuberculosis in Santiago de Cuba

Introducción: La tuberculosis es un problema de salud en el mundo, por lo que se necesitan métodos como el GeneXpert para realizar un diagnóstico rápido y seguro. Objetivo: Determinar la precisión del GeneXpert como método para el diagnóstico de la tuberculosis en Santiago de Cuba en relación con los estudios tradicionales. Métodos: Se efectuó un estudio descriptivo y transversal desde diciembre de 2018 hasta igual mes de 2019 de 31 pacientes a quienes se les realizaron los 3 métodos para el diagnóstico de la tuberculosis. Se utilizaron variables, tales como edad, sexo, muestras estudiadas, positividad de los métodos utilizados, así como concordancia entre el GeneXpert y el cultivo mediante el índice de Kappa. Resultados: En la serie predominaron los pacientes mayores de 50 años (48,4 %), el sexo masculino (66,7 %) y el esputo como muestra más representativa (80,6 %); asimismo, el cultivo resultó positivo en 32,3 % y el GeneXpert en 22,6 %. En tanto, se diagnosticó tuberculosis en 11 pacientes y el índice de Kappa fue de 0,58. Conclusiones: La determinación de GeneXpert en el diagnóstico de la tuberculosis es precisa, dada su sensibilidad y especificidad altas en relación con los estudios tradicionales de esputo y cultivo, lo cual se confirmó por la elevada concordancia del índice de Kappa.

Introduction: Tuberculosis is a health problem worldwide, reason why methods as the GeneXpert are needed to carry out a quick and safe diagnosis. Objective: To determine the accuracy of GeneXpert as a method for the diagnosis of tuberculosis in Santiago de Cuba in connection with the traditional studies. Methods: A descriptive and cross-sectional study was carried out from December, 2018 to the same month in 2019 of 31 patients to whom the 3 methods for the diagnosis of tuberculosis were carried out. Some variables were used, such as age, sex, studied samples, positivity of the used methods, as well as consistency between the GeneXpert and the culture by means of the Kappa index. Results: In the series there was a prevalence of the patients over 50 years (48.4 %), male sex (66.7 %) and sputum as more representative sample (80.6 %); also, the culture was positive in 32.3 % and GeneXpert in 22.6 %. As long as, tuberculosis was diagnosed in 11 patients and the Kappa index was 0.58. Conclusions: The determination of GeneXpert in the diagnosis of tuberculosis is necessary, given its high sensibility and specificity in connection with the traditional studies of sputum and culture, which was confirmed due to the high consistency of the Kappa index.

Simulación de dosis absorbida en terapia molecular mediante método de Montecarlo utilizando software libre GEANT4: GATE

RESUMEN Fundamento: aún no existe una forma óptima para determinar la dosis absorbida por los tumores; este desconocimiento es la causa de que la dosis final del tratamiento sea impredecible. Por esta causa los pacientes pueden estar recibiendo dosis mayores que las mínimas requeridas para su correcto diagnóstico. Objetivo: crear un código fuente para un proyecto de aplicación del programa GATE en la simulación de la dosis absorbida en radioterapia molecular, por método Montecarlo, para un maniquí de Giap. Métodos: se realizó la simulación por método de Montecarlo a partir de modelar el maniquí de Giap, mediante la plataforma de simulación GATE. Se compararon los resultados obtenidos con la información reflejada en la bibliografía sobre las mejores prácticas estandarizadas. Resultados: se confeccionó un código fuente implementado en GATE para la determinación de la dosis absorbida en radioterapia molecular. Se obtuvo distribución no uniforme de dosis en un medio de actividad uniforme y un 2 % de incertidumbre aproximado (en buena correspondencia con los valores reportados en la literatura), los resultados permiten afirmar que la simulación de dosis por medio de la plataforma GATE es confiable, de poco gasto computacional y altamente recomendable. Conclusiones: es recomendable utilizar la plataforma GATE para la simulación del cálculo de la dosis absorbida por ser rápida, de bajo costo computacional y confiable.

ABSTRACT Background: there is still no optimal way to determine the dose absorbed by tumors; this lack of knowledge is the reason why the final dose of treatment is unpredictable. For this reason, patients may be receiving doses greater than the minimum required for their correct diagnosis. Objective: to create a source code for an application project of the GATE program in the simulation of absorbed dose in molecular radiotherapy, by Monte Carlo method, for a Giap phantom. Methods: the simulation was carried out by the Montecarlo method from modeling the Giap phantom, using the GATE simulation platform. The results obtained were compared with the information reflected in the bibliography on standardized best practices. Results: a source code implemented in GATE was prepared for the determination of the absorbed dose in molecular radiotherapy. Non-uniform distribution of doses was obtained in a medium with uniform activity and an approximate 2% uncertainty (in correspondence with the values reported in the literature), the results allow to affirm that the dose simulation through the GATE platform is reliable, of little computational expense and highly recommended. Conclusions: it is advisable to use the GATE platform for the simulation of the calculation of the absorbed dose because it is fast, of low computational cost and reliable.

Validity and reliability of a computer-assisted system method to measure axial vertebral rotation.

Background: Axial vertebral rotation and Cobb's angle are essential parameters for analysing adolescent idiopathic scoliosis. This study's scope evaluates the validity and absolute reliability of application software based on a new mathematical equation to determine the axial vertebral rotation in digital X-rays according to Raimondi's method in evaluators with different degrees of experience. Methods: Twelve independent evaluators with different experience levels measured 33 scoliotic curves in 21 X-rays with the software on three separate occasions, separated one month. Using the same methodology, the observers re-measured the same radiographic studies three months later but on X-ray films and in a conventional way. Results: Both methods show good validity and reliability, and the intraclass correlation coefficients are almost perfect. According to our results, the software increases 1.7 times the validity and 1.9 times the absolute reliability of axial vertebral rotation on digital X-rays according to Raimondi's method, compared to the conventional manual measurement. Conclusions: The intra-group and inter-group agreement of the measurements with the software shows equal or minor variations than with the manual method, among the different measurement sessions and in the three experience groups. There is almost perfect agreement between the two measurement methods, so the equation and the software may be helpful to increase the accuracy in the axial vertebral rotation assessment.

Pressurized liquid extraction to obtain chia seeds oils extracts enriched in tocochromanols. Nanoemulsions approaches to preserve the antioxidant potential.

The objective of this study was to use accelerated-solvent-extraction to achieve antioxidant extracts from chia seeds oils, enriched in tocopherols and tocotrienols, namely tocochromanols. Nanotechnology applications have been also incorporated to develop an innovative formulation of chia seeds oil nanoemulsion that preserve its antioxidant potential after conditions of oxidative stress. Chia seeds oils proved to be a valuable source of tocochromanols, from 568.84 to 855.98 µg g-1, depending on the geographical provenance. Quantitative data obtained by LC-DAD-ESI-MS/MS showed outstanding levels of γ-Tocopherol, over 83%, followed far behind by Tocopherols-(α, ß, δ) and Tocotrienols-(α, ß, δ, γ)-tocotrienols. The characteristic tocochromanols fingerprint of chia seeds oils was positively correlated with the FRAP and DPPH antioxidant activity of the extracts (between 18.81 and 138.48 mg Trolox/g). Formulation of the Chia seeds oils as nanoemulsions did not compromised the antioxidant properties of fresh extracts. Interestingly, nanoemulsions retained about the 80% of the initial antioxidant capacity after UV-induced stress, where the non-emulsified oils displayed a remarkable reduction (50-60%) on its antioxidant capacity under the same conditions. These antioxidant chia seeds formulations can constitute a promising strategy to vectorizing vitamin E isomers, in order to be used for food fortification, natural additives and to increase the self-life of food products during packing.

Arritmia ventricular maligna asociada a un gossypiboma: reporte de un caso / Malignant ventricular arrhythmia associated to gossypiboma: clinical case report / Arritmia ventricular maligna vinculada a gossypiboma: reporte de um caso clínico

Un gossypiboma, oblitoma o textiloma se define como todo cuerpo extraño olvidado en el interior de un paciente durante una intervención quirúrgica. Representa una complicación posquirúrgica poco frecuente pero de consecuencias potencialmente graves. En general, se manifiesta con cuadros clínicos variables: una masa o pseudotumor, sangrados, fiebre, dolor, varios meses o años después de la cirugía original. También puede ser un hallazgo accidental. Describimos el caso clínico de una paciente con un gossypiboma vinculado a una cirugía cardíaca que se realizó 40 años antes al cuadro clínico actual, que se presenta con arritmia ventricular maligna.

A gossypiboma, oblitoma or textiloma is defined as a surgical object left in the interior of the body after surgery. It represents an uncommon but potentially life threatening post-surgery complication. Clinical manifestations are variable and depend on location, relations and size, from pseudo-tumoral masses, bleeding, fever, pain and other nonspecific presentations. The onset of symptoms is unpredictable, occurring from months or years after surgery. Patients may course asymptomatically and be diagnosed incidentally as an imaging finding. We describe a case of a patient with gossypiboma diagnosed 40 years after undergoing cardiac surgery, who presented with a malignant ventricular arrhythmia.

Um gossypiboma, oblitoma ou textiloma está definido como todo corpo estranho esquecido no interior de um paciente durante um procedimento cirúrgico, representando uma complicação pos cirúrgica pouco frequente, mas com consequências potencialmente graves. Geralmente, se manifesta com quadros clínicos variáveis: uma massa ou pseudotumor, sangramentos, febre, dor, varios meses ou anos após a cirurgia original ou ser um hachado acidental. Descrevemos o caso clínico de uma paciente com um gossypiboma vinculado a uma cirurgia cardíaca realizada 40 anos antes do quadro clínico atual, que se apresenta com arritmia ventricular maligna.

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk Human papillomavirus (HPV) infection. Despite improved outcomes in non-metastatic ASCC, definitive chemoradiotherapy constitutes the standard treatment for localized disease. Evidences for predictive and prognostic biomarkers are limited. Here, we performed a viral, immune, and mutational characterization of 79 non-metastatic ASCC patients with complete definitive chemoradiotherapy. HPV-16 was detected in 91% of positive cases in single infections (78%) or in coinfections with multiple genotypes (22%). Fifty-four percent of non-metastatic ASCC cases displayed mutations affecting cancer driver genes such as PIK3CA (21% of cases), TP53 (15%), FBXW7 (9%), and APC (6%). PD-L1 expression was detected in 57% of non-metastatic ASCC. Increased PD-L1 positive cases (67%) were detected in patients with complete response compared with non-complete response to treatment (37%) (p = 0.021). Furthermore, patients with PD-L1 positive tumors were significantly associated with better disease-free survival (DFS) and overall survival (OS) compared with patients with PD-L1 negative tumors (p = 0.006 and p = 0.002, respectively). PD-L1 expression strongly impacts CR rate and survival of non-metastatic ASCC patients after standard definitive chemoradiotherapy. PD-L1 expression could be used to stratify good versus poor responders avoiding the associated morbidity with abdominal perineal resection.

Effects of Cannabis Consumption on Sleep.

Despite the fact that medical properties of Cannabis have been recognized for more than 5000 years, the use of Cannabis for medical purposes have recently reemerged and became more accessible. Cannabis is usually employed as a self-medication for the treatment of insomnia disorder. However, the effects of Cannabis on sleep depend on multiple factors such as metabolomic composition of the plant, dosage and route of administration. In the present chapter, we reviewed the main effect Cannabis on sleep. We focused on the effect of "crude or whole plant" Cannabis consumption (i.e., smoked, oral or vaporized) both in humans and experimental animal models.The data reviewed establish that Cannabis modifies sleep. Furthermore, a recent experimental study in animals suggests that vaporization (which is a recommended route for medical purposes) of Cannabis with high THC and negligible CBD, promotes NREM sleep. However, it is imperative to perform new clinical studies in order to confirm if the administration of Cannabis could be a beneficial therapy for the treatment of sleep disorders.

Baseline prevalence and type distribution of Human papillomavirus in sexually active non-vaccinated adolescent girls from Argentina.

In 2011, Argentina launched a government-funded national Human papillomavirus (HPV) immunization program incorporating a bivalent HPV vaccine, with a 0-1-6-month schedule, for girls 11 years of age, born after January 2000. Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs. However, the data on HPV prevalence at young ages are very limited. The aim of this work was to determine the prevalence of HPV infection and type-specific distribution in sexually active 15-17-year-old non-vaccinated girls. Cervical samples from 1073 adolescents were collected for HPV detection and genotyping using the BSGP5+/GP6+PCR-reverse line blot (RLB) assay. Out of 957 specimens analyzed, 56.3% were positive for any HPV type; 42.2% harbored at least one high-risk HPV (HR-HPV) type and 30.8% low-risk HPV (LR-HPV) types. Multiple and single infections were identified in 36.3% and 20.0% of the samples respectively. The 6 most common HR-HPV types were HPV16 (11.1%), HPV52 (10.8%), HPV56 (8.3%), HPV51 (7.4%), HPV58 (7.3%) and HPV31 (7.1%). The prevalence of HR-HPV-16/18 was 15.2%. In conclusion, results confirm that HPV (particularly HR-types) are very common among sexually active adolescents, and prevalence rises quickly after their sexual debut. Our HPV type-specific prevalence baseline may be used to monitor post-vaccinal longitudinal changes in Argentina.

Development of a hyperimmune equine serum therapy for COVID-19 in Argentina

The disease named COVID-19, caused by the SARS-CoV-2 coronavirus, is currently generating a global pandemic. Vaccine development is no doubt the best long-term immunological approach, but in the current epidemiologic and health emergency there is a need for rapid and effective solutions. Convalescent plasma is the only antibody-based therapy available for COVID-19 patients to date. Equine polyclonal antibodies (EpAbs) put forward a sound alternative. The new generation of processed and purified EpAbs containing highly purified F(ab’)2 fragments demonstrated to be safe and well tolerated. EpAbs are easy to manufacture allowing a fast development and scaling up for a treatment. Based on these ideas, we present a new therapeutic product obtained after immunization of horses with the receptor-binding domain of the viral Spike glycoprotein. Our product shows around 50 times more potency in in vitro seroneutralization assays than the average of convalescent plasma. This result may allow us to test the safety and efficacy of this product in a phase 2/3 clinical trial to be conducted in July 2020 in the metropolitan area of Buenos Aires, Argentina.

La enfermedad denominada COVID-19 es causada por el coronavirus SARS-CoV-2 y es actualmente considerada una pandemia a nivel global. El desarrollo de vacunas es sin duda la mejor estrategia a largo plazo, pero debido a la emergencia sanitaria, existe una necesidad urgente de encontrar soluciones rápidas y efectivas para el tratamiento de la enfermedad. Hasta la fecha, el uso de plasma de convalecientes es la única inmunoterapia disponible para pacientes hospitalizados con COVID-19. El uso de anticuerpos policlonales equinos (EpAbs) es otra alternativa terapéutica interesante. La nueva generación de EpAbs incluyen el procesamiento y purificación de los mismos y la obtención de fragmentos F(ab’)2 con alta pureza y un excelente perfil de seguridad en humanos. Los EpAbs son fáciles de producir, lo cual permite el desarrollo rápido y la elaboración a gran escala de un producto terapéutico. En este trabajo mostramos el desarrollo de un suero terapéutico obtenido luego de la inmunización de caballos utilizando el receptor-binding domain de la glicoproteína Spike del virus. Nuestro producto mostró ser alrededor de 50 veces más potente en ensayos de seroneutralización in vitro que el promedio de los plasmas de convalecientes. Estos resultados nos permitirían testear la seguridad y eficacia de nuestro producto en ensayos clínicos de fase 2/3 a realizarse a partir de julio de 2020 en la zona metropolitana de Buenos Aires, Argentina.

Catálogo actualizado de las plantas vasculares del Parque Nacional Isla del Coco, Costa Rica

Introducción: La flora de la Isla del Coco ha sido objeto de diversos esfuerzos de recolecta, estudios y publicaciones desde hace más de 300 años, hasta llegar a registrarse 263 especies; no obstante, una exploración reciente permitió determinar que se han presentado muchos cambios nomenclaturales, de clasificación y de incremento de especies desde la última publicación, lo cual hace necesario la publicación de una lista actualizada de especies. Objetivo: Elaborar un catálogo actualizado de las plantas vasculares de la Isla del Coco. Métodos: Mediante la búsqueda y revisión de ejemplares de herbario, publicaciones y recolecta de plantas entre 2016 y 2017, se elaboró una lista actualizada de plantas de la isla. Además, se determinó la riqueza estimada y la calidad del inventario utilizando estimadores de biodiversidad y la proporción de especies de acuerdo a su forma, hábitat epífito y procedencia. Resultados: Se registraron 296 especies de plantas vasculares, en 199 géneros y 82 familias, lo cual representa alrededor de un 80 % de la diversidad esperada según los estimadores utilizados (Chao-1 y ecuación de Clench). Del total, 219 (74%) especies son nativas y 77 (26%) son introducidas. Las especies nativas incluyen angiospermas (53%), helechos (44%) y licófitos (3%) y las introducidas solo angiospermas. Se indican las familias y géneros más diversos y las especies más comunes o abundantes. Se presenta un endemismo del 22% (48 spp.) de la flora nativa, compuesto principalmente por helechos (58%). La flora presenta una alta proporción de especies herbáceas (63%) y una baja representación de especies arborescentes (12%) y de bejucos y enredaderas (8%). También se presenta una alta proporción de epífitas, con un 20% del total de la flora, compuesto mayormente por helechos (69%). Este estudio adicionó 45 nuevas especies a la isla, de las cuales 16 son especies nuevas para la ciencia y endémicas para la isla y ocho son especies introducidas. También se actualizaron o corrigieron 36 nombres de especies en comparación con Trusty et al. (2006). Se proporciona un catálogo de especies con anotaciones. Conclusiones: La flora de la Isla del Coco presenta ciertas particularidades que la distinguen de otras islas oceánicas del Pacífico, en especial por la alta proporción de helechos endémicos y la alta diversidad de este grupo en general y el porcentaje relativamente bajo de endemismo. También es característico la baja diversidad de especies arbóreas, con una alta dominancia de Sacoglottis holdridgei en todos los bosques de la Isla y la alta proporción de especies epífitas, compuesto principalmente por helechos. La proporción de especies introducidas es relativamente baja en comparación con otras islas oceánicas del Pacífico.

Introduction: The flora of Isla del Coco has been the subject of various collection studies and publications efforts for more than 300 years. During these years 263 species were registered; however, there have been nomenclature and classification changes, and an increase of known species since the last publication. Objective: To prepare an updated catalog of the vascular plants of Isla del Coco. Methods: The catalog present here is based on the review of herbarium specimens, publications, and plants collected between 2016 and 2017 by the authors. An updated list of plants on the island was prepared. In addition, the estimated richness and the quality of the inventory were determined through biodiversity estimators and the proportion of species according to their form, epiphytic habitat, and origin. Results: 296 species of vascular plants were registered, corresponding to 199 genera and 82 families, which represents about 80% of the expected diversity according to the estimators used (Chao-1 and Clench equation). Of the total, 219 (74%) species are native and 77 (26%) are introduced. Native species include angiosperms (53%), ferns (44%) and lycophytes (3%), and those introduced are represented only by angiosperms. The most diverse families and genera and the most common or abundant species are indicated. From the native flora, 48 spp. (22%) are endemic, and is mainly composed of ferns (58%). The flora has a high proportion of herbaceous species (63%) and a low representation of arborescent species (12%) and vines (8%). There is also a high proportion of epiphytes (20% of the total flora), mostly composed of ferns (69%). This study added 45 new species records to the island, of which 16 are new species for science and endemic to the island, and eight are introduced species. Thirty-six species names were updated or corrected compared to Trusty et al. (2006). A catalog of species with annotations is provided. Conclusions: The flora of Isla del Coco presents certain peculiarities that distinguish it from other Pacific oceanic islands, especially due to the high proportion of endemic ferns, and the high diversity of this group in general, and the relatively low percentage of endemism. Also, characteristics as the low diversity of tree species, with high dominance of Sacoglottisholdridgei in all the forests of the island, and the high proportion of epiphytic species, mainly composed of ferns. The proportion of introduced species is relatively low, compared to other oceanic Pacific islands.

Diabetes mellitus tipo 1: edad de comienzo y presencia en familiares de primer grado / Type 1 diabetes mellitus: age of onset and presence in first-degree relatives

Introducción: la diabetes mellitus tipo 1 (DM1) se considera una enfermedad de la infancia/adolescencia, pero puede ocurrir a cualquier edad. El riesgo de desarrollar DM1 es de ocho a 15 veces mayor en parientes de primer grado. La proporción de menores de 15 años con un pariente de primer grado afectado es ≈12%. Luego de años de seguimiento, esta frecuencia puede aumentar a más del 20%. Objetivos: determinar la edad de comienzo en pacientes adultos con DM1 y su frecuencia en familiares de primer grado. Materiales y métodos: en 414 sujetos se definió diagnóstico de DM1 por fenotipo, juicio clínico y requerimiento de insulina dentro del año de diagnóstico. Se determinó edad al diagnóstico y los sujetos se dividieron en mayores y menores de 30 años al momento del debut. En ellos se evaluó y comparó: DM1 en familiares de primer grado, índice de masa corporal (IMC), circunferencia de cintura, HbA1c e hipotiroidismo. Para la comparación de variables cuantitativas de los dos grupos se usó test de t y ANOVA para grupos múltiples, y para las variables categóricas se empleó chi cuadrado con corrección de Fisher. Resultados: el debut antes de los 10 años fue de 28,2%, entre los 10 y 20 años de 36,9%, entre los 20 y 30 años de 18,8% y por encima de los 30 años de 17,1%. Hubo similar frecuencia de hipotiroidismo y familiares de primer grado con DM1 en aquellos con diagnóstico antes o después de los 30 años. Se halló presencia de DM1 en familiares de primer grado en el 17,2% (padre 3,6%, madre 3,1%, hermano 10,2%, hijo 0,5%). Conclusiones: antes de los 30 años debutó el 82,9% de los pacientes, pero hubo un 17,1% que lo hizo después. El 17,2% tenía familiares de primer grado con DM1. A diferencia de los estudios en niños y adolescentes, y al igual que los estudios que evaluron poblaciones de DM1 adultos, encontramos el mayor antecedente de DM1 entre hermanos (10,2%). Dicho patrón familiar fue similar entre DM1 con comienzo antes o después de los 30 años

Introduction: type 1 diabetes mellitus (T1DM) is a childhood and adolescence disease, but it can occur at any age. The risk of developing T1DM is 8-15 times higher in first-degree relatives of patients with T1DM. The proportion of affected first-degree relatives in children under 15 with T1DM is ≈12%. This frequency may increase to more than 20% after years of follow-up. Objectives: to determine the age of onset of T1DM in adult patients and the frequency of T1DM in their first-degree relatives. Materials and methods: a diagnosis of T1DM was defined in 414 subjects by phenotype, clinical judgment and early insulin requirement within the year of diagnosis. Age at diagnosis was determined and subjects were divided into those with debut before or after 30. The following variables were recorded and compared: presence of T1DM in first-degree relatives, body mass index (BMI), waist circumference, HbA1c and association with hypothyroidism. t test and ANOVA for two or multiple subgroups comparison and chi square test with Fisher correction for quantitative or categorical variables were used. Results: the frequency of diabetes debut before the age of 10 was 28.2%, between 10 and 20 years 36.9%, between 20 and 30 years 18.8% and above 30 years 17.1%. The frequency of hypothyroidism and first-degree relatives with T1DM was similar in those diagnosed before or after 30 years. The presence of T1DM in first-degree relatives was found in 17.2% of the patients (father 3.6%, mother 3.1%, sibling 10.2%, son 0.5%). Conclusions: in 82.9% of patients debut was before the age of 30, but it was later in 17.1%. 17.2% of patients had first-degree relatives with T1DM. We found the highest frequency of T1DM association among siblings (10.2%) similar to studies in adult T1DM populations but contrary to studies in children and adolescents. This family pattern was similar between T1DM beginning before or after 30 years

Tomografía por emisión de positrones con 18F-fluordeoxiglucosa-tomografía computarizada en el diagnóstico del tumor primario de origen desconocido / Value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ın the diagnosis of carcinoma of unknown primary origin

Introducción: La incidencia de tumores primarios de origen desconocido en pacientes oncológicos es del 0,5 al 7 por ciento en el momento del diagnóstico con una supervivencia a los 3 y 5 años de 11 y 6 por ciento, respectivamente. Objetivo: valorar la utilidad de la técnica PET/CT-FDG (Tomografía por emisión de positrones con 18F-Fluordeoxiglucosa) en el diagnóstico de tumor primario de origen desconocido (TOD). Material y método: Se analizaron retrospectivamente los estudios PET/CT-FDG realizados en pacientes con el diagnóstico de TOD para la búsqueda de tumor primario, con estudios convencionales previos negativos, entre noviembre de 2017 y junio de 2018. El diagnóstico final se estableció mediante confirmación histológica y/o seguimiento clínico/radiológico por 8 meses. Resultados: 42 pacientes fueron estudiados, en 19 estudios PET/CT se evidenciaron focos de captación sugestivos de tumor primario, de los cuales 9 se confirmaron histológicamente como verdaderos positivos y sólo 1 correspondió a un falso positivo. De los 23 pacientes con PET/CT negativos para tumor primario, todos continuaron con diagnóstico de TOD a pesar de las múltiples pruebas diagnósticas. Conclusiones: La técnica PET/CT permitió identificar el 45,2 por ciento de los tumores primarios en la muestra de pacientes, lo que la convierte en una herramienta útil para el diagnóstico en pacientes con metástasis de origen desconocido. Se considera que el PET/CT-FDG debe ser incluido de manera precoz en los algoritmos diagnósticos en Cuba, permitiendo orientar la realización de pruebas complementarias subsiguientes(AU)

Introduction: The incidence of carcinoma of unknown primary origin in oncologic patients is from 0,5 percent to 7 percent at the time of diagnosis with an overall 3-year and 5-year survival of 11 percent and 6 percent, respectively. Objective: To assess the effectiveness of 18 F-FDG-PET/CT (18F-fluorodeoxyglucose posıtron emıssıon tomography) in the diagnosis of carcinoma of unknown primary origin (CUP). Material and Methods: F-FDG-PET/CT studies were conducted in patients with CUP in the search for primary tumor with negative previous conventional studies carried out from November, 2017 to June 2018. The final diagnosis was established by histological confirmation and/or clinical/radiological follow-up during 8 months. Results: A total of 44 patients were studied. There were evidences of suggestive CUP in 19 patients; 9 of them were histologically confirmed as true-positive and only 1 was a false-positive. Of the 23 patients with negative F-FDG-PET/CT studies for primary tumor, all of them continued with the diagnosis of CUP in spite of multiples diagnostic tests. Conclusions: The FDG-PET/CT technique allowed to identify 45,2 percent of the primary tumors in this study, which demonstrates that it is very useful tool for the diagnosis of metastases of unknown origin. It is considered that F-FDG-PET/CT studies should be included earlier in the diagnostic algorithms in Cuba, which will allow to indicate subsequent complementary tests(AU)

Collaborative Cardiac Care: A Comprehensive Heart Team Approach to Multiple Severe Vascular Conditions.

Left main artery coronary disease represents the highest risk lesion of ischemic heart disease. Revascularization can be accomplished by surgery or percutaneous interventions. This study highlights the case of a patient with severe multiple peripheral vascular conditions and complex coronary anatomy treated with percutaneous coronary intervention using mechanical circulatory support. (Level of Difficulty: Intermediate.).

Indoor radon in Spanish workplaces. A pilot study before the introduction of the European Directive 2013/59/Euratom.

OBJECTIVE: To explore whether there is a possible problem regarding indoor radon concentration surpassing the new European Directive 2013/59/Euratom threshold in Spanish workplaces. We also aim to find out whether radon concentration might be associated with certain characteristics of workplaces. METHOD: We performed a cross-sectional study to measure indoor radon concentrations in Spanish workplaces including five different sectors (education, public administration, the health sector, the tourist sector and the private sector). To be measured, the workplace should be occupied permanently by at least one worker. Alpha-track type radon detectors were placed for at least three months and read at the Galician Radon Laboratory at the University of Santiago de Compostela. A descriptive analysis was performed on radon distribution by sector, building characteristics and number of workers affected. RESULTS: We faced enormous difficulties in finding volunteers for this study. Galicia and Madrid had the highest number of measurements. Of a total of 248 measurements, 27% had concentrations above 300 Bq/m3. Median radon concentration was 251 Bq/m3 in Galicia, followed by Madrid, with 61.5 Bq/m3. Forty-six percent of the workplaces measured in Galicia had radon concentrations higher than 300 Bq/m3 followed by 10.6% in Madrid. Nineteen percent of all workers were exposed to more than 300 Bq/m3 and 6.3% were exposed to radon concentrations higher than 500 Bq/m3. CONCLUSION: Indoor radon exposure might be a relevant problem in Spanish workplaces and the number of affected workers could be high. The prevalence of workers exposed to high radon concentrations probably depends on the geographical area.