Thiopurines in inflammatory bowel disease. How to optimize thiopurines in the biologic era?

Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed. © Copyright © 2021 Gargallo-Puyuelo, Laredo and Gomollón

Ground state representations of loop algebras

Let g be a simple Lie algebra, Lg be the loop algebra of g. Fixing a point in S^1 and identifying the real line with the punctured circle, we consider the subalgebra Sg of Lg of rapidly decreasing elements on R. We classify the translation-invariant 2-cocycles on Sg. We show that the ground state representation of Sg is unique for each cocycle. These ground states correspond precisely to the vacuum representations of Lg.Comment: 22 pages, no figur

Tratamiento de fracturas diafisarias inestables de fémur con clavo intramedular encerrojado tipo FMRP

Un grupo de 26 fracturas conminutas de fémur, rotacionalmente inestables, fueron tratadas con clavo intramedular encerrojado tipo FMRP. En 22 casos la conminución afectaba a más del 50% de la cortical. Del total de enclavados, 22 fueron estáticos y 4 dinámicos. La consolidación desde el punto de vista clínico y radiológico ocurrió en el 92% de los casos. En 2 casos se desarrolló un pseudoartrosis. Sólo un paciente mostró un acortamiento mayor de 1 cm. Una angulación mayor de 10° en cualquiera de los planos del espacio fue apreciada en 5 pacientes. No se produjo en ningún caso deformidad rotacional. El clavo intramedular encerrojado ha aumentado las indicaciones del enclavado intramedular en el tratamiento de las fracturas inestables de fémur. La incidencia de infección y pseudoartrosis es baja. La estabilidad del montaje permite una movilización inmediata del paciente, rehabilitación temprana y menor estancia intrahospitalaria. El clavo FMRP disminuye el tiempo de fluoroscopia, un fresado con instrumentos flexibles y es más barato que otros sistemas similares.Twenty six comminuted and rotationally unstable fractures of the femur were treated with the FMBP intramedullary locked nail. Twenty two of the fractures had comminution involving more than 50% of the cortex. Of the nailings, 22 were static and 4 dynamic. Clinical and radiographic union occurred in 92% of cases. There were 2 nonunions. There was one case of deep wound infection. Only one patient had a shortening greater than 1 cm. Angulation in any plane greater than 10° was noted in 5 patients. There were no instances of rotatory deformities. The interlocking nail has expanded the indications for the use of closed intramedullary nailing in the treatment of unstable femoral fractures. The incidence of infection and nonunion is low. Stability of the fractures allows immediate mobilization of the patients, early rehabilitation of the limb and shorter hospital stay. The FMRP nail eliminated fluoroscopy, flexible reamers and is cheaper as compared to other systems

Spectral triples and the super-Virasoro algebra

We construct infinite dimensional spectral triples associated with representations of the super-Virasoro algebra. In particular the irreducible, unitary positive energy representation of the Ramond algebra with central charge c and minimal lowest weight h=c/24 is graded and gives rise to a net of even theta-summable spectral triples with non-zero Fredholm index. The irreducible unitary positive energy representations of the Neveu-Schwarz algebra give rise to nets of even theta-summable generalised spectral triples where there is no Dirac operator but only a superderivation.Comment: 27 pages; v2: a comment concerning the difficulty in defining cyclic cocycles in the NS case have been adde

Bloqueo atrioventricular completo en un perro : tratamiento mediante la implantación de un marcapasos endovenosos permanente

Una perra Labrador Retriever presentaba una historia de síncopes, fatiga e intolerancia al ejercicio debida a un bloqueo atrioventricular completo. Debido a que no respondía a la terapia médica (terbutalina, teofilina y posteriormente atropina), fue remitida al Hospital Clínico Veterinario de la Universidad de Murcia con el fin de considerar la implantación de un marcapasos. Las radiografías de tórax mostraron aumento global de la silueta cardiaca y la ecocardiografía puso de manifiesto, además, ligera regurgitación de válvulasatrioventriculares. Se le implantó un marcapasos endovenoso permanente unipolar con modo VVI bajo anestesia general, guiando el cable hacia el ventrículo derecho mediante fluoroscopia con amplificador de imagen. Ocho meses después de la implantación, no se han producido complicaciones y el marcapasos funciona según los parámetros programados.

Limits of Gaudin algebras, quantization of bending flows, Jucys--Murphy elements and Gelfand--Tsetlin bases

Gaudin algebras form a family of maximal commutative subalgebras in the tensor product of $n$ copies of the universal enveloping algebra U(\g) of a semisimple Lie algebra \g. This family is parameterized by collections of pairwise distinct complex numbers $z_1,...,z_n$. We obtain some new commutative subalgebras in U(\g)^{\otimes n} as limit cases of Gaudin subalgebras. These commutative subalgebras turn to be related to the hamiltonians of bending flows and to the Gelfand--Tsetlin bases. We use this to prove the simplicity of spectrum in the Gaudin model for some new cases.Comment: 11 pages, references adde