Resistance mechanism to fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma.

Precision medicine is a major achievement that has impacted on management of patients diagnosed with advanced cholangiocarcinoma (CCA) over the last decade. Molecular profiling of CCA has identified targetable alterations, such as fibroblast growth factor receptor-2 (FGFR-2) fusions, and has thus led to the development of a wide spectrum of compounds. Despite favourable response rates, especially with the latest generation FGFRi, there are still a proportion of patients who will not achieve a radiological response to treatment, or who will have disease progression as the best response. In addition, for patients who do respond to treatment, secondary resistance frequently develops and mechanisms of such resistance are not fully understood. This review will summarise the current state of development of FGFR inhibitors in CCA, their mechanism of action, activity, and the hypothesised mechanisms of resistance.

An Analytic Equation for Assessing the Thickness of Titanium Nitride Coatings by Energy Dispersive X-ray Spectroscopy in the Scanning Electron Microscope.

In this study, a methodology for assessing the thickness of titanium nitride (TiN) coatings by energy dispersive X-ray spectroscopy (EDS) in the scanning electron microscope is explored. A standardless method is applied, where the film thickness (th) is related to the microscope accelerating voltage (V0), the type of substrate and the ratio between the more intense peaks in the EDS spectrum, arising from both the substrate and the coating (afterwards called the I-ratio, IR). Three different substrates covered with TiN were studied, namely, silicon, glass, and stainless steel. Monte Carlo simulations enabled to state an analytic equation, which allows assessing the coating thickness as follows:th=thcr⋅exp[-ßIR1/n]where IR = Iksubstrate/Ikcoating, thcr (critical thickness) is the largest coating thickness, which is assessable at a fixed V0, ß is a multiplication factor, and n is an exponent, where thcr, ß and n are assessable from V0 and substrate type. Interpolation via the equation presented, using reference thicknesses, allowed thickness predictions with around 80% of datapoints differing less than around 2% from the reference value. A procedure for detecting variations as low as 1.0% in coating thickness regarding the nominal thickness is presented.

Accuracy of a reference-free Monte Carlo approach for SEM-EDS thickness assessment of TiN coatings onto diverse substrates.

Energy dispersive spectroscopy (EDS) experiments were carried out in the scanning electron microscope (SEM) on top of either stainless steel (SS), silicon or glass substrates covered with TiN nitride coatings. The nominal coating thicknesses were 0.43, 1.1, 2.1 and 3.0 µm. From the EDS spectra obtained, the ratio between the strongest peak coming from the substrate and the Tik peak, from the coating, was assessed at an increasing microscope accelerating voltage (V0) between 10 and 30 kV. This ratio is afterward called Intensity-ratio (IR). A methodology was developed for assessing the coating thickness from the experimental IR and the V0 by using Monte Carlo simulations of the dispersion of electrons inside the covered samples and the concomitant emission of characteristic X-ray photons. Three freeware Monte Carlo graphical user interfaces were used, and the predicted thicknesses were compared between them, namely Casino, MC-Xray and DTSA. At fixed V0, numerical simulations predict a mono-valued and smooth relationship between IR and coating thickness. Monte Carlo predictions on the coating thickness were compared with reference thicknesses independently assessed by cross-sectional micrographs obtained in the SEM. Absolute value of percentage discrepancy between the predicted and the reference thicknesses was lower than 30 %, wherein the lower the V0, the less accurate the predicted thickness. In general, none of the three pieces of software compared outperformed the others, although predicted thicknesses significantly varied between them. For V0 higher than 20 kV, 90 % of predicted thicknesses deviated less than 15 % from the reference value. Predicted thicknesses for TiN coatings onto Si substrates presented the largest discrepancy regarding reference values.

Análisis clínico y citogenético de un caso de trastorno del desarrollo sexual testicular XX con SRY negativo / Clinical and Cytogenetic Analysis of a Case of SRY-Negative XX Testicular Disorder of Sex Development / Análise clínica e citogenética de um caso de transtorno do desenvolvimento sexual testicular XX com SRY-negativo

Resumen: El trastorno del desarrollo sexual (TDS) testicular XX es una patología que se presenta en un individuo con cariotipo 46,XX con un fenotipo anatómico de genitales externos masculinos, que pueden variar desde la normalidad hasta la ambigüedad genital. Clínicamente se han descrito dos subgrupos de hombres 46,XX con SRY-negativos y SRY-positivos, dependiendo de la presencia o no del gen SRY que normalmente se encuentra en el cromosoma Y participando en la determinación testicular. En este artículo se describen los antecedentes personales y los hallazgos clínicos de un infante con anomalías del meato urinario en el cual se identificó un complemento cromosómico 46,XX. También, se realizó hibridación in situ fluorescente en linfocitos de sangre periférica que demostró la ausencia del gen SRY y confirmó la presencia de dos cromosomas X.

Abstract XX testicular disorder of sex development (DSD) is a pathology that occurs in an individual with a 46,XX karyotype and an anatomical phenotype of male external genitalia, which may vary from normal to ambiguous. Clinically, two subgroups of SRY-negative and SRY-positive, 46, XX men have been described, depending on the presence of the SRY gene that is normally found on the Y chromosome participating in testicular determination. This article describes the personal history and clinical findings of an infant with urethral meatus abnormalities in whom a 46,XX chromosome set was identified. Also, fluorescent in situ hybridization was performed in peripheral blood lymphocytes which demonstrated the absence of the SRY gene and confirmed the presence of two X chromosomes.

Resumo: O transtorno do desenvolvimento sexual (TDS) testicular XX é uma patologia apresentada em um indivíduo com cariótipo 46,XX com um fenótipo anatômico de genitais externos masculinos, que podem variar da normalidade à ambiguidade genital. Clinicamente, são descritos dois subgrupos de homens 46,XX com SRY-negativos e SRY-positivos, dependendo da presença ou não do gene SRY que normalmente se encontra em Y cromossomo participando da determinação testicular. Neste artigo, são descritos os antecedentes pessoais e os achados clínicos de uma criança com anomalias de meato urinário em que foi identificado um complemento cromossômico 46,XX. Além disso, foi rea -lizada hibridação in situ fluorescente em linfócitos de sangue periférico que demonstrou a ausência do gene SRY e confirmou a presença de dois cromossomos X.

Malformación cavernosa hipotalámica: presentación de caso / Hypothalamic cavernous malformation: case report

Los cavernomas (también llamados hemangiomas cavernosos) son malformaciones vasculares de localización inusual en el hipotálamo. En este artículo se presenta el caso de una mujer de 23 años que consultó al servicio de urgencias del Hospital Universitario de San Ignacio, con una semana de evolución de cefalea intensa, sin antecedentes de importancia y con examen físico normal. Se realizó inicialmente una escanografía cerebral simple y luego una resonancia magnética con gadolinio. Se encontró una lesión localizada en el hipotálamo, con angiografía cerebral normal. Fue intervenida quirúrgicamente y se obtuvo la confirmación patológica de cavernoma hipotalámico.

Linfangioma macroquístico en el brazo: presentación de caso / Case report: macrocystic lymphangioma of the arm

En este artículo se reseña el caso de una malformación linfática macroquística en el brazo derecho de un niño de 3 años de edad, quien desde el nacimiento presentó la masa en estudio. La ecografía y la resonancia magnética fueron consistentes con una malformación linfática macroquística, y el estudio histopatológico posterior a la resección total confirmó el hallazgo. Estas lesiones son frecuentes en la cabeza y el cuello; pero rara vez se presentan en las extremidades.