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Introducción: El linfoma de células T intestinal epiteliotrópico monomórfico es una neoplasia derivada de linfocitos intraepiteliales. La etiología es desconocida, pero se ha asociado a enfermedad celíaca o a síndrome de malabsorción, aunque en la actualidad se considera un linfoma esporádico. La histopatología se caracteriza por linfocitos de tamaño intermedio a pequeño, con mínimo pleomorfismo, que generalmente expresan CD8 y CD56. Reporte de caso: Mujer de 60 años con un cuadro de dispepsia de larga evolución, ingresada por dolor abdominal agudo, diarrea, nausea, vómito bilioso y pérdida de peso. En los estudios se determinó anemia microcítica hipocrómica y desequilibrio hidroelectrolítico. Se evidenció por tomografía de abdomen una lesión nodular esplénica y engrosamiento concéntrico segmentario de yeyuno e íleon distal asociado a la presencia de líquido libre en cavidad abdominal. Evolución: Se realizó una laparotomía exploratoria con resección de yeyuno-transverso anastomosis latero-lateral, en patología se deteminó la presencia de 3 tumores: a nivel de yeyuno de 16x8.5x6 cm, en el íleon distal de 13x6.5x3 cm y en el ciego de 5x4x2cm con histología de linfoma no Hodgkin T de alto grado, intestinal primario, de tipo monomórfico epiteliotrópico (MEITL). Fue dada de alta en mejores condiciones diez días después. Dos semanas luego del alta desarrollo sepsis de foco urinario, deshidratación por síndrome de intestino corto, hiperamonemia y neumonía de focos múltiples con derrame pleural bilateral. Falleció al sexto día de hospitalización. Conclusiones: En conclusión, el MEITL es una neoplasia agresiva primaria intestinal de reciente identificación y pobre pronóstico. No se conocen en su totalidad los mecanismos moleculares y genéticos asociados a esta entidad. El caso presentado demostró un curso clínico similar al reportado en la literatura.

Introducción: La aparición de nuevas técnicas de imagen y mayor conocimiento de esta entidad han contribuido para que el diagnóstico del Tumor Mucinoso Papilar Intraductal haya aumentado en la última década. En el presente artículo describimos un caso de un paciente con Tumor Mucinoso Papilar Intraductal de páncreas, hallazgo incidental en Tomografía computarizada de abdomen. Caso Clínico: Se trata de una mujer de 71 años de edad, con antecedentes de Diabetes tipo 2, Hipertensión Arterial Esencial, y cáncer de mama intervenida. En un estudio de control con tomografía computarizada de abdomen se observó un tumor pancreático de 3 x 1.1 cm. Se realizó una punción transagástrica, con lo que se obtuvo una muestra para estudio patológico, el cual reportó una neoplasia mucinosa papilar intraductal. Evolución: La paciente fue sometida a cirugía con la Técnica de Whipple, con duodenopancreatectomía, en donde se retiró la cabeza del páncreas con el tumor adyacente. El estudio de patología confirmó una neoplasia mucinosa papilar intraductal. La paciente no presentó complicaciones post-operatorias y continúa en revisión en consulta externa. Conclusión: Por tratarse de una lesión maligna, el diagnóstico oportuno y correcto fue importante en este caso, para la conducta terapéutica quirúrgica resolutiva.

Resumen: La pandemia COVID ha hecho de las consultas telemáticas una herramienta básica en la práctica diaria. El objetivo principal del estudio es valorar los resultados de la aplicación de consultas telemáticas para limitar la movilidad de los pacientes.Son objetivos operativos: proponer un plan de consultas, conocer cómo limita la asistencia a las consultas, definir qué patologías se benefician más con este plan. Material y métodos: Se propone un esquema con la creación de consultas previas a las agendadas para valorar idoneidad y posibilidad de realizarla en acto único no presencial. Resultados: Se han realizado 5.619 consultas con una falta de respuesta telefónica del 19%. El 74% de los pacientes fueron resueltos de forma virtual. Existe diferencia entre unidades, siendo más probable la respuesta telefónica para las consultas de unidad, OR = 0,60 o de traumatología general, OR = 0,67 y menos para los derivados desde urgencias.El 20% de las consultas no se acompañaban de pruebas complementarias. Las consultas de traumatología general, OR = 0,34, control postoperatorio, OR = 0,49, y unidades, OR = 0,40, cumplieron mejor este requisito. De los pacientes restantes, las consultas de traumatología general, OR = 0,50, y las derivadas a unidades, OR = 0,54 fueron las que más se resolvieron sin acudir presencialmente. Conclusiones: Se han resuelto de forma no presencial el 74% de los pacientes que atendieron a la llamada telefónica. El 20% de los pacientes acuden a la visita sin pruebas complementarias. Las consultas de seguimiento de osteosíntesis y postoperatorio de cirugía artroscópica son las que más precisan de ser realizadas de forma presencial. Abstract: The COVID pandemic has made telematic consultations a basic tool in daily practice. Aims: The main objective of the study is to assess the results of the application of telematic consultations to limit the mobility of patients. The operational objectives are; to propose a consultation plan, to know how attendance limits consultations and to define which pathologies benefit the most from this plan. Methods: A scheme is proposed with the creation of pre-scheduled clinic to assess suitability and the possibility of carrying them out in a single non face-to-face act. Results: Phone call to 5,619 patients were made with a lack of response of 19%.The cases of 74% of the patients that answered were resolved virtually. There is a difference between units, obtaining a higher answering rate from patients appointed to specific clinic units, OR = 0.60, or to general trauma ones, OR = 0.67. The lowest answering rate was obtained from those derived from the emergency department. Twenty per cent of the consultations were not accompanied by complementary tests that would have favored the resolution in a single act. The general trauma consultations, OR = 0.34, postoperative control, OR = 0.49, and specific unit ones, OR = 0.40, were the ones that better met this requirement. Out of the remaining patients, the general trauma consultations, OR = 0.50, and those referred to units, OR = 0.54, were the ones that had a higher resolution rate without in- person consultation. Conclusions: The cases of 74% of the patients who answered the phone call were resolved virtually. Cases of 20% of the patients cannot be solved in a single act because they are derived without complementary tests.Osteosynthesis and postoperative arthroscopic follow-up consultations are the ones that need to be carried out in person the most.

Non-covalent polymer-protein conjugation is emerging as a potential route to improve pharmacokinetics and pharmacodynamics of protein therapeutics. In this study, a family of structurally related block copolymers of mPEG2k - poly(glutamic acid) with linear A-B (mPEG2k-lin-polyGA) and miktoarm A-B3 ((mPEG2k-mik-(polyGA)3) structure was synthesised by N-carboxyanhydride (NCA) ring-opening polymerisation to assess the effect of macromolecular topology of the copolymers on polymer-protein complexation. The data illustrate that the synthesised copolymers are capable of complexing a model protein, lysozyme, at optimal pH conditions through non-covalent interactions, with complexation efficiencies depending on the copolymers composition and molecular architecture. In native gel electrophoresis experiments, linear mPEG2k-lin-GA10 copolymer, possessing a short polyanionic polyGA block, shows a low level of complexation, which does not change when the number of polyGA branches of the same size is increased, using a miktoarm mPEG2k-mik-(GA10)3 copolymer. However, enhanced complexation is observed when the same number of ionisable GA units (30) are displayed on a linear macromolecular scaffold; mPEG2k-mik-(GA10)3 vs. mPEG2k-lin-GA30. Again complexation efficiency did not increase when the number of complexing polyGA branches were increased; mPEG2k-lin-GA30 vs. mPEG2k-mik-(GA30)3. Nanoparticle tracking analysis (NTA) showed that the copolymer-protein complexes possessed hydrodynamic diameters in the 50-200 nm range, suggesting a degree of control in the assembly process. Sequestration of lysozyme within polymer complexes resulted in a decrease in its apparent enzymatic activity, which was re-established on the complexes dissociation upon a treatment with competitive complexant. Intrinsic fluorescence and circular dichroism (CD) studies suggested structural conformation of the protein was not altered following complexation with mPEG2k-polyGA copolymers. Taken together, these results provide an initial structure-function relationship for protein-complexing mPEG2k-polyGA copolymers with variable macromolecular topology, opening the way for their future application in biological and biomedical studies.

Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes with a new ‘complexing excipient’ - vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200 nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B12-internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B12 receptor-mediated cellular internalization of B12-targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2–3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B12-targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B12-targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue., SCOPUS: ar.j, info:eu-repo/semantics/published

The self?assembly of specific polymers into well?defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high?throughput method to screen the ability of polymers to self?assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96?well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high?throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.

Pulmonary delivery of protein therapeutics has considerable clinical potential for treating both local and systemic diseases. However, poor protein conformational stability, immunogenicity and protein degradation by proteolytic enzymes in the lung are major challenges to overcome for the development of effective therapeutics. To address these, a family of structurally related copolymers comprising polyethylene glycol, mPEG2k, and poly(glutamic acid) with linear A-B (mPEG2k-lin-GA) and miktoarm A-B3 (mPEG2k-mik-(GA)3) macromolecular architectures was investigated as potential protein stabilisers. These copolymers form non-covalent nanocomplexes with a model protein (lysozyme) which can be formulated into dry powders by spray-drying using common aerosol excipients (mannitol, trehalose and leucine). Powder formulations with excellent aerodynamic properties (fine particle fraction of up to 68%) were obtained with particle size (D50) in the 2.5 µm range, low moisture content (

Sterosomes (STEs), a new and promising non-phospholipidic liposome platform based on palmitic acid (PA) and cholesterol (Chol) mixtures, need to have polyethylene glycol (PEG) chains grafted to their surface in order to obtain long-circulating nanocarriers in the blood stream. A post-insertion method was chosen to achieve this modification. The post-insertion process of PEG-modified distearoylphosphoethanolamine (DSPE-PEG) was monitored using the zeta potential value of STEs. Various conditions including PEG chain length and the DSPE-PEG/PA-Chol ratio, were explored. Zeta potential of STEs changed from about −40 mV for non-modified STEs to values close to 0 mV by the end of the process, i.e. for PEG-modified STEs. The kinetics of DSPE-PEG insertion and the stability of the resulting PEG-modified STEs were not considerably influenced, within the investigated range, by changes in PEG chain lengths and in DSPE-PEG/PA-Chol proportion. The post-insertion of PEG chains reduced in vitro complement activation as well as in vitro macrophage uptake compared to the non-modified STEs. Moreover, longer blood circulation time in mice was established for PEG-modified STEs intravenously injected compared to non-modified STEs. These results establish that post-insertion process of PEG chains to STEs is a promising strategy for developing long-term circulating drug delivery nanocarriers. Fil: Cieślak, Anna. University Of Angers; Francia Fil: Wauthoz, Nathalie. University Of Angers; Francia. Université Libre de Bruxelles; Bélgica Fil: Nieto Orellana, Alejandro. University Of Angers; Francia Fil: Lautram, Nolwenn. University Of Angers; Francia Fil: Béjaud, Jérôme. University Of Angers; Francia Fil: Hureaux, José. University Of Angers; Francia Fil: Lafleur, Michel. University of Montreal; Canadá Fil: Benoit, Jean-Pierre. University Of Angers; Francia Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Bastiat, Guillaume. University Of Angers; Francia

The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.

Hypothesis Liposomes made of single-chain amphiphiles and a large amount of sterols display several advantages including a limited permeability. In the present paper, we examine the possibility to prepare such non-phospholipid liposomes with interfacial polyethylene glycol (PEG) in order to improve their circulation in the blood stream. Cholesterol (Chol) was chosen as the PEG anchor. Experiments The phase behavior of mixtures of palmitic acid (PA) and cholesterol including various proportions of PEGylated cholesterol (PEG-Chol) was characterized. In conditions leading to the formation of fluid bilayers, properties of the resulting liposomes were assessed. Findings Up to 20 mol% of PEGylated cholesterol could be introduced without significant perturbations in fluid bilayers made of PA and cholesterol. With 10 mol% PEG-Chol, PA/Chol/PEG-Chol liposomes showed a very limited permeability to calcein and doxorubicin. Doxorubicin could be actively loaded in PA/Chol/PEG-Chol liposomes with a high drug loading efficiency and a high drug to lipid ratio. Pharmaco-kinetic experiments in rats indicated that interfacial PEG reduced the clearance of PA/Chol liposomes compared to the naked ones. However the lifetime of these non-phospholipid liposomes in the blood circulation was considerably shorter than that observed for control PEGylated phospholipid liposomes, a phenomenon associated with the negative interfacial charge of the PA/Chol/PEG-Chol liposomes.