The cardiovascular pathologist in the aortic team.

Aortic diseases require a multidisciplinary management for diagnosis, treatment and follow-up with better outcomes in referral centers using a team-based approach. The setting up of a multi-disciplinary aortic team for the discussion of complex cases has been already proposed; it is also supported by the ACC/AHA. Surgeons and radiologists, more or less other physicians such as cardiologists, geneticists, rheumatologists/internal medicine specialists and pathologists are involved into such a team. The role of the cardiovascular pathologist is to examine the aortic specimens, to diagnose and classify the aortic lesions. Herein, the role of the pathologist in the aortic team is discussed and the pathobiology of aortic diseases is reviewed for reference by pathologists. The aortic specimens are mainly obtained from emergency or elective surgical procedures on the thoracic aorta, less frequently from organ/tissue (including cardiac or heart valve) donors, post-mortem procedures or abdominal aortic surgery. In the last decade, together with the progress of medical sciences, the histological definitions and classifications of the aortic pathology are undergoing thorough revisions that are addressed to an etiopathogenetic approach because of possible clinico-pathological correlations, therapeutic and prognostic impact. Pathologists may also have an important role in research and teaching. Therefore, histological analyses of the aortic specimens require adequate sample processing and pathologist expertise because histology contributes to definite diagnosis, correct management of patients and even (in genetic diseases) families, but also to research in the challenging field of aortopathies.

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma.

The impact of tumor microenvironment (TME) in influencing clinical response to first-line immune checkpoint inhibitor (ICI)-based treatment in advanced renal cell carcinoma (RCC) is unclear. Immunohistochemistry (IHC) could identify biomarkers related to immune checkpoints and immune cell population. This study retrospectively characterized TME from 28 RCC patients who received first line ICI-based therapy through IHC assessment of selected markers and explored preliminary evidence about their possible correlation with treatment efficacy. We found a significantly higher count of CD80+, CD163+ cells and their ratio in RCC with clear cell component compared to those without clear cell features; additionally, patients with metastatic disease at diagnosis were associated with higher expression of CD163+ cells, while higher count of CD4+ cells and CD4+/CD8+ ratio were found in RCC with sarcomatoid features. Patients achieving partial or complete response were associated with lower expression of CD163+ cells (median 28 vs 47; p = 0.049). Furthermore, lower expression of CD163+ was associated with better PFS (median PFS 20.0 vs 4.7 months; HR 0.22 p = 0.011) and OS (median OS NR vs 14.4 months; HR 0.28 p = 0.036). A longer OS was reported in PD-L1 CPS negative patients (median OS NR vs 11.8 months; HR 0.20 p = 0.024). High infiltration of CD163+ macrophages, who typically present "anti-inflammatory" M2-like phenotype, could identify a subgroup of patients with poor survival after receiving first-line ICI.

The Cellular Dysfunction of the Brain-Blood Barrier from Endothelial Cells to Astrocytes: The Pathway towards Neurotransmitter Impairment in Schizophrenia.

Schizophrenia (SCZ) is an articulated psychiatric syndrome characterized by a combination of genetic, epigenetic, and environmental factors. Our intention is to present a pathogenetic model combining SCZ alterations and the main cellular actors of the blood-brain barrier (BBB): endothelial cells (ECs), pericytes, and astrocytes. The homeostasis of the BBB is preserved by the neurovascular unit which is constituted by ECs, astrocytes and microglia, neurons, and the extracellular matrix. The role of the BBB is strictly linked to its ability to preserve the biochemical integrity of brain parenchyma integrity. In SCZ, there is an increased BBB permeability, demonstrated by elevated levels of albumin and immunoglobulins in the cerebrospinal fluid, and this is the result of an intrinsic endothelial impairment. Increased BBB permeability would lead to enhanced concentrations of neurotoxic and neuroactive molecules in the brain. The pathogenetic involvement of astrocytes in SCZ reverberates its consequences on BBB, together with the impact on its permeability and selectivity represented by the EC and pericyte damage occurring in the psychotic picture. Understanding the strict interaction between ECs and astrocytes, and its consequent impact on cognition, is diriment not only for comprehension of neurotransmitter dyshomeostasis in SCZ, but also for focusing on other potential therapeutic targets.

The Cerebellum's Role in Affective Disorders: The Onset of Its Social Dimension.

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are the most frequent mental disorders whose indeterminate etiopathogenesis spurs to explore new aetiologic scenarios. In light of the neuropsychiatric symptoms characterizing Cerebellar Cognitive Affective Syndrome (CCAS), the objective of this narrative review is to analyze the involvement of the cerebellum (Cbm) in the onset of these conditions. It aims at detecting the repercussions of the Cbm activities on mood disorders based on its functional subdivision in vestibulocerebellum (vCbm), pontocerebellum (pCbm) and spinocerebellum (sCbm). Despite the Cbm having been, for decades, associated with somato-motor functions, the described intercellular pathways, without forgiving the molecular impairment and the alteration in the volumetric relationships, make the Cbm a new important therapeutic target for MDD and BD. Given that numerous studies have showed its activation during mnestic activities and socio-emotional events, this review highlights in the Cbm, in which the altered external space perception (vCbm) is strictly linked to the cognitive-limbic Cbm (pCbm and sCbm), a crucial role in the MDD and BD pathogenesis. Finally, by the analysis of the cerebellar activity, this study aims at underlying not only the Cbm involvement in affective disorders, but also its role in social relationship building.

Tumor Progression from a Fibroblast Activation Protein Perspective: Novel Diagnostic and Therapeutic Scenarios for Colorectal Cancer.

In 2020, the Global Cancer Observatory estimated the incidence of colorectal cancer (CRC) at around 10.7% coupled with a mortality rate of 9.5%. The explanation for these values lies in the tumor microenvironment consisting of the extracellular matrix and cancer-associated fibroblasts (CAFs). Fibroblast activation protein (FAP) offers a promising target for cancer therapy since its functions contribute to tumor progression. Immunohistochemistry examination of FAP, fibronectin ED-B, and CXCR4 in primary tumors and their respective synchronous and/or metachronous metastases along with semiquantitative analysis have been carried out on histological samples of 50 patients diagnosed with metastatic CRC. The intensity of FAP, articulated by both "Intensity %" and "Intensity score", is lower in the first metastasis compared to the primary tumor with a statistically significant correlation. No significant correlations have been observed regarding fibronectin ED-B and CXCR4. Tumors that produce FAP have an ambivalent relationship with this protein. At first, they exploit FAP, but later they reduce its expressiveness. Although our study has not directly included FAP-Inhibitor (FAPI) PET/CT, the considerable expression of FAP reveals its potential as a diagnostic and therapeutic tool worthy of further investigation. This dynamic relationship between cancer and FAP has substantial diagnostic and therapeutic implications.

Astrocytes as Neuroimmunocytes in Alzheimer's Disease: A Biochemical Tool in the Neuron-Glia Crosstalk along the Pathogenetic Pathways.

This work aimed at assessing Alzheimer's disease (AD) pathogenesis through the investigation of the astrocytic role to transduce the load of amyloid-beta (Aß) into neuronal death. The backbone of this review is focused on the deepening of the molecular pathways eliciting the activation of astrocytes crucial phenomena in the understanding of AD as an autoimmune pathology. The complex relations among astrocytes, Aß and tau, together with the role played by the tripartite synapsis are discussed. A review of studies published from 1979 to 2023 on Scopus, PubMed and Google Scholar databases was conducted. The selected papers focused not only on the morphological and metabolic characteristics of astrocytes, but also on the latest notions about their multifunctional involvement in AD pathogenesis. Astrocytes participate in crucial pathways, including pruning and sprouting, by which the AD neurodegeneration evolves from an aggregopathy to neuroinflammation, loss of synapses and neuronal death. A1 astrocytes stimulate the production of pro-inflammatory molecules which have been correlated with the progression of AD cognitive impairment. Further research is needed to "hold back" the A1 polarization and, thus, to slow the worsening of the disease. AD clinical expression is the result of dysfunctional neuronal interactions, but this is only the end of a process involving a plurality of protagonists. One of these is the astrocyte, whose importance this work intends to put under the spotlight in the AD scenario, reflecting the multifaceted nature of this disease in the functional versatility of this glial population.

Short report. Cooking for autism: a pilot study of an innovative culinary laboratory for Italian adolescents and emerging adults with autism spectrum disorder.

BACKGROUND: Adolescence and emerging adulthood are critical periods for young people with autism spectrum disorder (ASD). However, there is a lack of appropriate and affordable services available. AIMS: The Il Tortellante® is an Italian project aimed at promoting adaptive behavior and social skills, and at reducing the severity of symptomatology through a culinary group intervention in which young people with ASD learn to make fresh pasta by hand. METHODS: A longitudinal study was conducted. PROCEDURE: Before and after the intervention, 20 participants were assessed based on the severity of symptoms, social skills, and adaptive behaviors. OUTCOME AND RESULTS: According to our findings, severity of symptoms and daily living skills improved significantly. CONCLUSION: A culinary intervention may be useful for adolescents and young adults with ASD to improve daily living skills and reduce ASD-related symptomatology. IMPLICATION: Services and associations may consider developing a culinary laboratory for people with ASD to improve group intervention proposals for adolescents and emerging adults. WHAT THIS PAPER ADDS?: This paper offers one of the first investigations of the impact of a culinary laboratory on ASD symptoms, social skills, and adaptive behavior in adolescents and young adults diagnosed with ASD. This group intervention could contribute to expand the range of interventions targeted at adolescents and young adults with ASD, to reduce the severity of symptoms, and to promote adaptive behaviors.