Delayed immune-related hepatitis after 24 months of pembrolizumab treatment: a case report and literature review.

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) pathway have revolutionized cancer immunotherapy by enhancing the immune system's ability to combat cancer cells. However, this innovative approach comes with a distinctive set of challenges, as these therapies can lead to immune-related adverse events (irAEs) due to their mechanism of action. The most common irAEs involve the skin, gastrointestinal tract, liver, endocrine system, and lungs. These events can range from mild skin rashes to severe colitis, pneumonitis, or even autoimmune organ damage. These adverse effects usually appear with an average of 5-15 weeks from the start of treatment depending on the affected organ. This article presents a case report of a delayed related-mediated hepatitis, after 24 months of treatment with pembrolizumab and almost 3 months after its termination, and a review of the scientific literature on cases of delayed immune-related hepatitis caused by anti-PD1. This case highlights the importance of monitoring patients treated with immune checkpoint inhibitors after cessation as a growing number of patients stop treatment due to achieving durable responses.

Primary central nervous system Hodgkin lymphoma: A case report and review of the literature / Linfoma de Hodgkin primario del sistema nervioso central. Presentación de un caso y revisión de la literatura

Central nervous system (CNS) involvement in the context of relapsed/refractory Hodgkin lymphoma (HL) is a quite rare, but well-known complication. Nevertheless, primary CNS–HL is an exceedingly rare condition, which diagnosis is based on well-defined morphological and immunohistochemical features, in addition to isolated involvement of the CNS. In spite of limited casuistry (just over twenty cases reported in the literature), available data agree that primary and isolated CNS–HL, when treated with a combination of surgery followed by some form of adjuvant therapy (radiotherapy±chemotherapy), carries a better prognosis than those cases with CNS involvement in the context of relapsed/refractory HL or those with CNS non-Hodgkin lymphoma. We herein report a case of a 55-year-old female patient who was diagnosed with primary CNS–HL. The patient was treated with complete surgical resection followed by intrathecal chemotherapy and whole brain radiotherapy (WBRT), showing fourteen months of disease-free survival at the time of this case report. A review of the available literature is also presented (AU)

La afectación del sistema nervioso central (SNC) en pacientes con diagnóstico de linfoma de Hodgkin (LH) sistémico es una complicación muy poco frecuente, aunque bien definida. Sin embargo, el LH primario del SNC es una entidad extremadamente rara, cuyo diagnóstico precisa la identificación de un patrón morfológico e inmunohistoquímico específico, así como la afectación aislada del SNC. Pese a contar con una casuística muy limitada (apenas una veintena de casos publicados en la literatura) la bibliografía disponible coincide en que el LH con afectación primaria y aislada del SNC, cuando es tratado con cirugía y tratamiento adyuvante (radioterapia±quimioterapia), parece tener un mejor pronóstico que aquellos casos en los que la afectación del SNC se produce en el contexto de un LH sistémico o en el contexto de un linfoma no Hodgkin. En este artículo se presenta el caso de una mujer de 55 años con diagnóstico histopatológico de LH primario del SNC. La paciente fue sometida a una exéresis completa de la lesión y a tratamiento adyuvante con quimioterapia intratecal y radioterapia holocraneal, con una supervivencia libre de enfermedad hasta la fecha de 14 meses. Se presenta asimismo, la revisión de la literatura disponible (AU)

Primary central nervous system Hodgkin lymphoma: A case report and review of the literature.

Central nervous system (CNS) involvement in the context of relapsed/refractory Hodgkin lymphoma (HL) is a quite rare, but well-known complication. Nevertheless, primary CNS-HL is an exceedingly rare condition, which diagnosis is based on well-defined morphological and immunohistochemical features, in addition to isolated involvement of the CNS. In spite of limited casuistry (just over twenty cases reported in the literature), available data agree that primary and isolated CNS-HL, when treated with a combination of surgery followed by some form of adjuvant therapy (radiotherapy±chemotherapy), carries a better prognosis than those cases with CNS involvement in the context of relapsed/refractory HL or those with CNS non-Hodgkin lymphoma. We herein report a case of a 55-year-old female patient who was diagnosed with primary CNS-HL. The patient was treated with complete surgical resection followed by intrathecal chemotherapy and whole brain radiotherapy (WBRT), showing fourteen months of disease-free survival at the time of this case report. A review of the available literature is also presented.

Lung cancer patients with COVID-19 in Spain: GRAVID study.

INTRODUCTION: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. METHODS: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). RESULTS: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. CONCLUSIONS: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.

Temperature-controlled metal/ligand stoichiometric ratio in Ag-TCNE coordination networks.

The deposition of tetracyanoethylene (TCNE) on Ag(111), both at Room Temperature (RT, 300 K) and low temperatures (150 K), leads to the formation of coordination networks involving silver adatoms, as revealed by Variable-Temperature Scanning Tunneling Microscopy. Our results indicate that TCNE molecules etch away material from the step edges and possibly also from the terraces, which facilitates the formation of the observed coordination networks. Moreover, such process is temperature dependent, which allows for different stoichiometric ratios between Ag and TCNE just by adjusting the deposition temperature. X-ray Photoelectron Spectroscopy and Density Functional Theory calculations reveal that charge-transfer from the surface to the molecule and the concomitant geometrical distortions at both sides of the organic/inorganic interface might facilitate the extraction of silver atoms from the step-edges and, thus, its incorporation into the observed TCNE coordination networks.

Imaging the microanatomy of astrocyte-T-cell interactions in immune-mediated inflammation.

The role of astrocytes in the immune-mediated inflammatory response in the brain is more prominent than previously thought. Astrocytes become reactive in response to neuro-inflammatory stimuli through multiple pathways, contributing significantly to the machinery that modifies the parenchymal environment. In particular, astrocytic signaling induces the establishment of critical relationships with infiltrating blood cells, such as lymphocytes, which is a fundamental process for an effective immune response. The interaction between astrocytes and T-cells involves complex modifications to both cell types, which undergo micro-anatomical changes and the redistribution of their binding and secretory domains. These modifications are critical for different immunological responses, such as for the effectiveness of the T-cell response, for the specific infiltration of these cells and their homing in the brain parenchyma, and for their correct apposition with antigen-presenting cells (APCs) to form immunological synapses (ISs). In this article, we review the current knowledge of the interactions between T-cells and astrocytes in the context of immune-mediated inflammation in the brain, based on the micro-anatomical imaging of these appositions by high-resolution confocal microscopy and three-dimensional rendering. The study of these dynamic interactions using detailed technical approaches contributes to understanding the function of astrocytes in inflammatory responses and paves the way for new therapeutic strategies.

Molecular self-assembly at solid surfaces.

Self-assembly, the process by which objects initially distributed at random arrange into well-defined patterns exclusively due to their local mutual interactions without external intervention, is generally accepted to be the most promising method for large-scale fabrication of functional nanostructures. In particular, the ordering of molecular building-blocks deposited at solid surfaces is relevant for the performance of many organic electronic and optoelectronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs) or photovoltaic solar cells. However, the fundamental knowledge on the nature and strength of the intermolecular and molecule-substrate interactions that govern the ordering of molecular adsorbates is, in many cases, rather scarce. In most cases, the structure and morphology of the organic-metal interface is not known and it is just assumed to be the same as in the bulk, thereby implicitly neglecting the role of the surface on the assembly. However, this approximation is usually not correct, and the evidence gathered over the last decades points towards an active role of the surface in the assembly, leading to self-assembled structures that only in a few occasions can be understood by considering just intermolecular interactions in solid or gas phases. In this work we review several examples from our recent research demonstrating the apparently endless variety of ways in which the surface might affect the assembly of organic adsorbates.

Abordajes transesfenoidales endoscópicos de los adenomas hipofisarios: una revisión crítica de nuestra experiencia / Transphenoidal endoscopic approaches for pituitary adenomas: a critical review of our experience

Introducción: El abordaje quirúrgico de la región hipofisaria ha evolucionado desde las vías transcraneales, a las sublabiales y transseptales microscópicas hasta los abordajes endoscópicos actuales. Objetivos: El objetivo de este trabajo es exponer y reflexionar sobre nuestra experiencia en el abordaje transnasal transesfenoidal endoscópico de los tumores hipofisarios, con las modificaciones que hemos introducido para mejorar la exéresis del tumor y disminuir la iatrogenia. Material y métodos: A lo largo de 9 años hemos intervenido a 37 pacientes afectos de adenomas hipofisarios mediante abordaje transesfenoidal endoscópico. Utilizamos lentes de 0 y 30 grados, navegador óptico, instrumental habitual de endoscopia nasal y brazo articulado para fijación de la óptica en el tiempo neuroquirúrgico. Se accede a la celda hipofisaria mediante esfenoidotomía bilateral. Resultados: La neumatización esfenoidal ha sido suficiente en todos los pacientes. Las complicaciones postperatorias más frecuentes han sido la diabetes insípida y los transtornos endocrinológicos. Rinolicuorrea postoperatoria en un paciente. Secuela nasal definitiva ninguna. Tiempo medio de estancia hospitalaria 5 días. Conclusiones: El abordaje endoscópico guiado con el navegador aporta grandes ventajas: rapidez, seguridad, disminución de la iatrogenia, preservación de la vía aérea nasal. La resección de un fragmento de tabique nasal adyacente al rostrum mejora la manejabilidad de los instrumentos hacia los márgenes tumorales. La fijación del endoscopio estabiliza la visión y permite al segundo cirujano ayudar con más eficacia (AU)

Background: The surgical approach to the pituitary fossae has evolved from transcranial to sublabial and transseptal microscopic ones, up to the current transsphenoidal endoscopic approach. Objectives: To present our experience in the transnasal transsphenoidal approach for pituitary adenomas and the modifications introduced to improve tumoral resection and to lower iatrogenia. Material and methods: Over nine years, we operated on 37 patients with pituitary adenomas using the transsphenoidal endoscopic approach. We utilised optical lens of 0° (approach) and 30° (adenoma resection), optic navigator, surgical instruments for nasal endoscopic and pituitary surgery. During the neurosurgical step, the endoscope was fixed by an articulated arm. We acceded to the pituitary fossae by a bilateral sphenoidotomy. Results: Sphenoid pneumatisation was sufficient in all the patients. The more common postoperative complications were diabetes insipidus and endocrinology deficiencies. Postoperative rhinoliquorrhea affected only one patient. No alterations of nasal fossae were observed. Mean patient hospitalisation was five days. Conclusions: Transsphenoidal endoscopic approach guided by navigator gives significant advantages: Shorter operating time and fewer complications, greater safety and preservation of the nasal passages. Resecting the sphenoidal rostrum and a fragment of adjacent nasal septum improves surgical instrument management into the pituitary fossae and therefore adenoma resection. Endoscope fixation stabilises the vision and allows the second surgeon to help more effectively (AU)

[Transphenoidal endoscopic approaches for pituitary adenomas: a critical review of our experience]. / Abordajes transesfenoidales endoscópicos de los adenomas hipofisarios: una revisión crítica de nuestra experiencia.

BACKGROUND: The surgical approach to the pituitary fossae has evolved from transcranial to sublabial and transseptal microscopic ones, up to the current transsphenoidal endoscopic approach. OBJECTIVES: To present our experience in the transnasal transsphenoidal approach for pituitary adenomas and the modifications introduced to improve tumoral resection and to lower iatrogenia. MATERIAL AND METHODS: Over nine years, we operated on 37 patients with pituitary adenomas using the transsphenoidal endoscopic approach. We utilised optical lens of 0° (approach) and 30° (adenoma resection), optic navigator, surgical instruments for nasal endoscopic and pituitary surgery. During the neurosurgical step, the endoscope was fixed by an articulated arm. We acceded to the pituitary fossae by a bilateral sphenoidotomy. RESULTS: Sphenoid pneumatisation was sufficient in all the patients. The more common postoperative complications were diabetes insipidus and endocrinology deficiencies. Postoperative rhinoliquorrhea affected only one patient. No alterations of nasal fossae were observed. Mean patient hospitalisation was five days. CONCLUSIONS: Transsphenoidal endoscopic approach guided by navigator gives significant advantages: Shorter operating time and fewer complications, greater safety and preservation of the nasal passages. Resecting the sphenoidal rostrum and a fragment of adjacent nasal septum improves surgical instrument management into the pituitary fossae and therefore adenoma resection. Endoscope fixation stabilises the vision and allows the second surgeon to help more effectively.

Charge-transfer-induced structural rearrangements at both sides of organic/metal interfaces.

Organic/metal interfaces control the performance of many optoelectronic organic devices, including organic light-emitting diodes or field-effect transistors. Using scanning tunnelling microscopy, low-energy electron diffraction, X-ray photoemission spectroscopy, near-edge X-ray absorption fine structure spectroscopy and density functional theory calculations, we show that electron transfer at the interface between a metal surface and the organic electron acceptor tetracyano-p-quinodimethane leads to substantial structural rearrangements on both the organic and metallic sides of the interface. These structural modifications mediate new intermolecular interactions through the creation of stress fields that could not have been predicted on the basis of gas-phase neutral tetracyano-p-quinodimethane conformation.

An organic donor/acceptor lateral superlattice at the nanoscale.

A precise control of the nanometer-scale morphology in systems containing mixtures of donor/acceptor molecules is a key factor to improve the efficiency of organic photovoltaic devices. Here we report on a scanning tunneling microscopy study of the first stages of growth of 2-[9-(1,3-dithiol-2-ylidene)anthracen-10(9H)-ylidene]-1,3-dithiole, as electron donor, and phenyl-C61-butyric acid methyl ester, as electron acceptor, on a Au(111) substrate under ultrahigh vacuum conditions. Due to differences in bonding strength with the substrate and different interactions with the Au(111) herringbone surface reconstruction, mixed thin films spontaneously segregate into a lateral superlattice of interdigitated nanoscale stripes with a characteristic width of about 10-20 nm, a morphology that has been predicted to optimize the efficiency of organic solar cells.

Toma de decisiones en el paciente diagnosticado de tumor cerebral. A propósito de un caso clínico / Decision making process in patients with brain tumor. Concerning a case report

Justificación: La decisión sobre la alternativa terapéutica más conveniente, que corresponde al paciente asesorado por el equipo sanitario, se hace especialmente difícil en casos de mal pronóstico. Pacientes: Paciente joven con tumor cerebral, reintervenido en diversas ocasiones, al que se detecta una recidiva. Resultados: En contra de la opinión del equipo multidisciplinar, el paciente decide someterse a una reintervención, falleciendo a los cuatro meses presentado una calidad de vida aceptable. Conclusiones: Se plantea la necesidad, a través de un counselling adecuado, de permitir que el paciente escoja el resultado clínico preferido tras la transmisión clara de las distintas consecuencias de cada decisión y de la probabilidad de que cada una de ellas ocurra, evitando el uso de términos confusos, como la descripción técnica de procedimientos y las sugerencias globales sobre las decisiones. Se enfatiza el respeto a la autonomía del paciente, bajo condiciones de no maleficencia (AU)

The patient´s decisión regarding the most advisable therapeutic alterantive is difficult, speccially in patients with por prognosis. Patients: Young patient who was operated on several times by brain tumour and he was admitted again by tumour recurrence. Results: The patient preferred to be reoperated against the multidisciplinary team decision. His quality of life was acceptable gut the patient died four months later. Conclusion: We think that the patient could be able to choose the preferred therapeutic option after adequate counseling. Confusing term such as technical description should be avoided. We emphasize the respect to the patient´s autonomy under non-maleficent conditions (AU)