Non-invasive vulnerable plaque imaging: how do we know that treatment works?

Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution

Liposomal Doxorubicin, Vinblastine and Dacarbazine Plus Consolidation Radiotherapy of Residual Nodal Masses for Frontline Treatment in Older Adults With Advanced Stage Classic Hodgkin Lymphoma: Improved Outcome in a Multi-Center Real-Life Study

: In elderly patients with high-risk classic Hodgkin lymphoma (c-HL), we evaluated the impact of a new modality treatment without bleomycin, that is, liposomal doxorubicin (NPLD)-based regimen plus consolidation radiotherapy of residual nodal masses (RNMs), on overall survival (OS) and progression free survival (PFS). In this retrospective study (2013-2023) conducted in tertiary hospitals in the bay of Naples (Italy), 50 older adults (median age, 69 years; range, 60-89) with advanced stage c-HL received frontline treatment with MVD ± irradiation. MVD consisted of 25 mg/m2 of NPLD along with standard Vinblastine and Dacarbazine for a total of 6 cycles (twelve iv administrations, every 2 weeks) followed by radiation of RNMs with size ≥ 2.5 cm at computed tomography. Patients underwent MVD with a median dose intensity of 92%. At 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography (FDG-PET), 90% of patients (45/50 patients; one failed to perform final FDG-PET due to early death) reached complete responses. Altogether, 17 patients (34%) received consolidation radiotherapy of RNMs with Deauville score ≥ 3. At 5-year median follow-up, the OS and PFS of the entire population were 87.5% (95% confidence interval [CI], 78.7-97.4) and 81.6% (95% CI, 71.4-93.2), respectively. Eleven patients (22%) experienced grade ≥ 3 adverse events, and 4 of them required hospitalization. Our data suggest that in older adults with high-risk c-HL NPLD-driven strategy (without bleomycin) plus consolidation radiotherapy (if needed) may be a promising up-front option, to test in phase II clinical trials for improving survival incidence

Cross-linking of ICAM-1 induces co-signaling of an oxidative burst from mononuclear leukocytes.

Abstract Cell adhesion molecules were first described as accessory molecules simply to bridge one cell to another. More recently, it has been realized that these molecules also transmit signals from outside of the cell to inside. We show that cross-linking of the ICAM-1 on the cell membrane with anti-ICAM-1 mAb and F(ab')2 fragments of goat anti-MIgG in the presence of suboptimal levels of the bacterial peptide FMLP results in co-stimulation of an oxidative burst from CD14 expressing PBMCs. The amplitude of the oxidative response was less than the oxidative burst induced by CD18 cross-linking, whereas the response was more prolonged. On the other hand, cross-linking by anti-L-selectin mAb plus F(ab')2 fragments of goat anti-MIgG induced a minimal oxidative burst that was not significantly greater than the response generated by anti-L-selectin mAb alone. The addition of an excess of soluble ICAM-1 to compete for the anti-ICAM-1 mAb inhibits the oxidative burst in response to ICAM-1 cross-linking but not to CD18 cross-linking. These results suggest that ICAM-1 is capable of delivering a transmembrane signal into CD14-positive PBMC.</jats:p

A form of circulating ICAM-1 in human serum.

Abstract A circulating form of the usually membrane-bound intercellular adhesion molecule-1 (ICAM-1) was identified and characterized in normal human serum, and in sera from patients with leukocyte adhesion deficiency (LAD). The molecule, designated circulating ICAM-1 (cICAM-1) was detected and quantitated by sandwich ELISA. Levels of cICAM-1 in sera from normal individuals ranged from 100 to 200 ng/ml. Sera from LAD patients had elevated cICAM-1 levels ranging from 200 to 700 ng/ml. The elevated levels of cICAM-1 in LAD sera may be due to an inability to adsorb cICAM-1 to cell-bound LFA-1 or may be an indirect result of the pathology accompanying the syndrome. cICAM-1 bound to mAb specific for four distinct ICAM-1 epitopes localized in domains D1, D2, D4, and D5, and displayed similar molecular size properties as recombinant soluble ICAM-1 on FPLC size-exclusion chromatography. When immobilized via a domain D5-specific mAb, cICAM-1 mediated function (LFA-1)-dependent lymphocyte adhesion equivalent to sICAM-1. These data indicate that cICAM-1 contains most, if not all, of the five extracellular domains of membrane ICAM-1, as well as the ability to bind specifically to LFA-1. The cellular source of cICAM-1 appeared to be from mononuclear cells; only lymphoid cell lines or primary PBMC cultures had detectable levels of cICAM-1 in cell culture supernatants. Because cICAM-1 retains the ability to bind specifically to LFA-1, it may act to regulate cell adhesion by promoting de-adhesion. Alternatively, cICAM-1 may be the indirect consequence of inflammation or tissue damage. As such, the detection of cICAM-1 could be useful as a marker of inflammatory disease.</jats:p