CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic colorectal cancer (mCRC) with mismatch-repair deficiency or high microsatellite instability (dMMR-MSI-H). Unfortunately, a patient's subgroup did not benefit from immunotherapy. Caudal-related homeobox transcription factor 2 (CDX-2) would seem to influence immunotherapy's sensitivity, promoting the chemokine (C-X-C motif) ligand 14 (CXCL14) expression. Therefore, we investigated CDX-2 role as a prognostic-predictive marker in patients with mCRC MSI-H. We retrospectively collected data from 14 MSI-H mCRC patients treated with ICIs between 2019 and 2021. The primary endpoint was the 12-month progression-free-survival (PFS) rate. The secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and disease control rate (DCR). The PFS rate at 12 months was 81% in CDX-2 positive patients vs 0% in CDX-2 negative patients (p = 0.0011). The median PFS was not reached (NR) in the CDX-2 positive group versus 2.07 months (95%CI 2.07-10.8) in CDX-2 negative patients (p = 0.0011). Median OS was NR in CDX-2-positive patients versus 2.17 months (95% Confidence Interval [CI] 2.17-18.7) in CDX2-negative patients (p = 0.026). All CDX-2-positive patients achieved a disease response, one of them a complete response. Among CDX-2-negative patients, one achieved stable disease, while the other progressed rapidly (ORR: 100% vs 0%, p = 0.0005; DCR: 100% vs 50%, p = 0.02). Twelve patients received 1st-line pembrolizumab (11 CDX-2 positive and 1 CDX-2 negative) not reaching median PFS, while two patients (1 CDX-2 positive and 1 CDX-2 negative) received 3rd-line pembrolizumab reaching a median PFS of 10.8 months (95% CI, 10.8-12.1; p = 0.036). Although our study reports results on a small population, the prognostic role of CDX-2 in CRC seems confirmed and could drive a promising predictive role in defining the population more sensitive to immunotherapy treatment. Modulating the CDX-2/CXCL14 axis in CDX-2-negative patients could help overcome primary resistance to immunotherapy.

Advanced imaging and Crohn's disease: An overview of clinical application and the added value of artificial intelligence.

PURPOSE: The purpose of this narrative review is to describe the clinical applications of advanced computed tomography (CT) and magnetic resonance (MRI) techniques in patients affected by Crohn's disease (CD), giving insights about the added value of artificial intelligence (AI) in this field. METHODS: We performed a literature search comparing standardized and advanced imaging techniques for CD diagnosis. Cross-sectional imaging is essential for the identification of lesions, the assessment of active or relapsing disease and the evaluation of complications. RESULTS: The studies reviewed show that new advanced imaging techniques and new MRI sequences could be integrated into standard protocols, to achieve a reliable quantification of CD activity, improve the lesions' characterization and the evaluation of therapy response. These promising tools are: dual-energy CT (DECT) post-processing techniques, diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI), Magnetization Transfer MRI (MT-MRI) and CINE-MRI. Furthermore, AI solutions show a potential when applied to radiological techniques in these patients. Machine learning (ML) algorithms and radiomic features prove to be useful in improving the diagnostic accuracy of clinicians and in attempting a personalized medicine approach, stratifying patients by predicting their prognosis. CONCLUSIONS: Advanced imaging is crucial in the diagnosis, lesions' characterisation and in the estimation of the abdominal involvement in CD. New AI developments are promising tools that could support doctors in the management of CD affected patients.

Role of imaging in rare COVID-19 vaccine multiorgan complications.

As of September 18th, 2021, global casualties due to COVID-19 infections approach 200 million, several COVID-19 vaccines have been authorized to prevent COVID-19 infection and help mitigate the spread of the virus. Despite the vast majority having safely received vaccination against SARS-COV-2, the rare complications following COVID-19 vaccination have often been life-threatening or fatal. The mechanisms underlying (multi) organ complications are associated with COVID-19, either through direct viral damage or from host immune response (i.e., cytokine storm). The purpose of this manuscript is to review the role of imaging in identifying and elucidating multiorgan complications following SARS-COV-2 vaccination-making clear that, in any case, they represent a minute fraction of those in the general population who have been vaccinated. The authors are both staunch supporters of COVID-19 vaccination and vaccinated themselves as well.

Non-invasive coronary imaging in patients with COVID-19: A narrative review.

SARS-CoV-2 infection, responsible for COVID-19 outbreak, can cause cardiac complications, worsening outcome and prognosis. In particular, it can exacerbate any underlying cardiovascular condition, leading to atherosclerosis and increased plaque vulnerability, which may cause acute coronary syndrome. We review current knowledge on the mechanisms by which SARS-CoV-2 can trigger endothelial/myocardial damage and cause plaque formation, instability and deterioration. The aim of this review is to evaluate current non-invasive diagnostic techniques for coronary arteries evaluation in COVID-19 patients, such as coronary CT angiography and atherosclerotic plaque imaging, and their clinical implications. We also discuss the role of artificial intelligence, deep learning and radiomics in the context of coronary imaging in COVID-19 patients.

Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging.

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Review of imaging biomarkers for the vulnerable carotid plaque.

Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. As a result of the rapid technological evolution in medical imaging, several important steps have been taken in the field of carotid plaque imaging allowing us to visualize the carotid atherosclerotic plaque and its composition in great detail. For computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound scan, evidence has accumulated on novel imaging-based markers that confer information on carotid plaque vulnerability, such as intraplaque hemorrhage and lipid-rich necrotic cores. In terms of the imaging-based identification of individuals at high risk of stroke, routine assessments of such imaging markers are the way forward for improving current clinical practice. The current review highlights the main characteristics of the vulnerable plaque indicating their role in the etiology of ischemic stroke as identified by intensive plaque imaging.

Primary Pulmonary B-Cell Lymphoma: A Review and Update.

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.

Carotid plaque imaging profiling in subjects with risk factors (diabetes and hypertension).

Carotid artery stenosis (CAS) due to the presence of atherosclerotic plaque (AP) is a frequent medical condition and a known risk factor for stroke, and it is also known from literature that several risk factors promote the AP development, in particular aging, smoke, male sex, hypertension, hyperlipidemia, smoke, diabetes type 1 and 2, and genetic factors. The study of carotid atherosclerosis is continuously evolving: even if the strategies of treatment still depends mainly on the degree of stenosis (DoS) determined by the plaque, in the last years the attention has moved to the study of the plaque components in order to identify the so called "vulnerable" plaque: features like the fibrous cap status and thickness, the volume of the lipid-rich necrotic core and the presence of intraplaque hemorrhage (IPH) are risk factors for plaque rupture, that can be studied with modern imaging techniques. The aim of this review is to give a general overview of the principle histological and imaging features of the subcomponent of carotid AP (CAP), focalizing in particular on the features of CAP of patients affected by hypertension and diabetes (in particular type 2 diabetes mellitus).

The broad landscape of follicular lymphoma: Part II.

Follicular lymphoma is a neoplasm derived from follicle center B cells, typically both centrocytes and centroblasts, in variable proportions according to the lymphoma grading. The pattern of growth may be entirely follicular, follicular and diffuse and rarely completely diffuse. It represents the second most common non-Hodgkin lymphoma, after diffuse large B-cell lymphoma and it is the most common low-grade mature B-cell lymphoma in Western countries. In the majority of cases, follicular lymphoma is a nodal tumor, occurring in adults and is frequently associated with the translocation t(14;18)(q32;q21)/IGH-BCL2. However, in recent years the spectrum of follicular lymphoma has expanded and small subsets of follicular lymphoma, which differ from common follicular lymphoma, have been identified and included in the current 2017 WHO classification. The aim of our review is to describe the broad spectrum of follicular lymphoma, pointing out that the identification of distinct clinicopathological variants of follicular lymphoma is relevant for the patient outcomes and treatment.

The broad landscape of follicular lymphoma: Part I.

Follicular lymphoma is a neoplasm derived from follicle center B cells, typically both centrocytes and centroblasts, in variable proportions according to the lymphoma grading. The pattern of growth may be entirely follicular, follicular and diffuse, and rarely completely diffuse. It represents the second most common non-Hodgkin lymphoma, after diffuse large B-cell lymphoma and is the most common low-grade mature B-cell lymphoma in western countries. In the majority of cases, follicular lymphoma is a nodal tumor, occurring in adults and frequently associated with the translocation t(14;18)(q32;q21)/IGH-BCL2. However, in recent years the spectrum of follicular lymphoma has expanded and small subsets of follicular lymphoma, which differ from common follicular lymphoma, have been identified and included in the current 2017 WHO classification. The aim of our review is to describe the broad spectrum of follicular lymphoma, pointing out that the identification of distinct clinicopathological variants of follicular lymphoma is relevant for patient outcomes and choice of treatment.