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.

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.

[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.