Uncommon 18F-FDG-PET/CT findings in patients affected by limbic encephalitis: Hyper-hypometabolic pattern with double antibody positivity and migrating foci of hypermetabolism

Autoimmune limbic encephalitis (LE) is a rare disorder; its diagnosis can be challenging.We report two uncommon cases of LE evaluated by brain 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) positron emission tomography/ computed tomography describing themetabolic imaging patterns, which were different from those observed in previous studies: the first one presented an unprecedented 18F-FDG brain mixed pattern, involving also themidbrain, despite negative magnetic resonance imaging exams; the second one showed migrating foci of hypermetabolism, one of which turned into hypometabolism at a later examination

Role of PET and SPECT in the study of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis has been defined as a "heterogeneous group of neurodegenerative syndromes characterized by progressive muscle paralysis caused by the degeneration of motor neurons allocated in primary motor cortex, brainstem, and spinal cord." A comprehensive diagnostic workup for ALS usually includes several electrodiagnostic, clinical laboratory and genetic tests. Neuroimaging exams, such as computed tomography, magnetic resonance imaging and spinal cord myelogram, may also be required. Nuclear medicine, with PET and SPECT, may also play a role in the evaluation of patients with ALS, and provide additional information to the clinicians.This paper aims to offer to the reader a comprehensive review of the different radiotracers for the assessment of the metabolism of glucose (FDG), the measurement of cerebral blood flow (CBF), or the evaluation of neurotransmitters, astrocytes, and microglia by means of newer and not yet clinically diffuse radiopharmaceuticals

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy

We investigated whether baseline [F-18] Fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each F-18-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline F-18-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing (18)F-FDG PET/CT SUV quantification.

BACKGROUND: The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up. PATIENTS AND METHODS. Forty-nine patients with stage I–II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography ((18)F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated. RESULTS: There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9. CONCLUSIONS: In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence

Atypical lymphoproliferation progressing into B-cell lymphoma in rheumatoid arthritis treated with different biological agents: clinical course and molecular characterization.

10noA patient with rheumatoid arthritis (RA) developed an atypical lymphoproliferative disorder (LPD) after methotrexate and cyclosporine A, which regressed after suspension of both drugs. After subsequent treatment with rituximab, the LPD was still undetectable. Anti-tumor necrosis factor a therapy was used when the arthritis relapsed, but an aggressive B-cell non Hodgkin's lymphoma developed. Molecular analyses showed an oligoclonal B-cell expansion at the LPD step. A minor clone with significant sequence homology to B-cell lymphomas arising in Sjogren's syndrome and mixed cryoglobulinemia syndrome, given rise to the non-Hodgkin's lymphoma. Treatment of rheumatoid arthritis associated with lymphoproliferation represents a clinical challenge, and common pathogenetic pathways to lymphoma may occur in different autoimmune diseases.openopenQuartuccio, Luca; De Re, V.; Fabris, M; Marzotto, A.; Franzolini, N; Gasparotto, D.; Caggiari, L.; Ferraccioli, G.; Scott, Cathryn Anne; DE VITA, SalvatoreQuartuccio, Luca; De Re, V.; Fabris, M; Marzotto, A.; Franzolini, N; Gasparotto, D.; Caggiari, L.; Ferraccioli, G.; Scott, Cathryn Anne; DE VITA, Salvator

Humoral and T-Cell Mediated Response after the Third Dose of mRNA Vaccines in Patients with Systemic Lupus Erythematosus on Belimumab

Objective: To evaluate humoral and T-cell cellular-mediated immune response after three doses of SARS-CoV-2 mRNA vaccines in patients with systemic lupus erythematosus (SLE) under Belimumab. Patients and methods: 12 patients on Belimumab and 13 age-matched healthy volunteers were recruited. Patients were in remission or in low disease activity, and they were taking no corticosteroids or only low doses. None of the patients and controls had detectable anti-SARS-CoV-2 antibodies due to previous exposure to the virus. All the patients received three doses of mRNA anti-SARS-CoV-2 vaccines and the humoral and cellular-mediated response were tested 4 weeks after the second dose (T0), 6 months after the second dose (T1) and 4 weeks after the third dose (T2). Comparison with the control group was performed at time T0 (i.e., 4 weeks after the second dose). Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while cellular-mediated response was evaluated using the interferon-gamma release assay (IGRA). Results: A humoral response was documented in all the patients at T0 (median 459; IQR 225.25–758.5), but the antibody titer significantly declined from T0 to T1 (median 44.7; IQR: 30.3–202; p = 0.0066). At T2, the antibody titer significantly increased from T1 (median 2500; IQR: 2500–2500), and it was not different from T0 (respectively p < 0.0001, p = 0.66). Cellular-mediated response significantly declined from T0 to T1 (p = 0.003) but not from T0 to T2 (p = 0.3). No differences were found between patients and controls at T0 as regards both humoral and cellular responses (p = 1.0 and p = 0.09 for humoral and cellular responses, respectively). Conclusion: The third dose of mRNA COVID-19 vaccine can restore both humoral and cellular immune response in SLE patients on Belimumab

T Cell Therapy for Nasopharyngeal Carcinoma

Among the novel biologic therapeutics that will increase our ability to cure human cancer in the years to come, T cell therapy is one of the most promising approaches. However, with the possible exception of tumor-infiltrating lymphocytes therapy for melanoma, clinical trials of adoptive T-cell therapy for solid tumors have so far provided only clear proofs-of-principle to build on with further development. Epstein-Barr virus (EBV)-associated malignancies offer a unique model to develop T cell-based immune therapies, targeting viral antigens expressed on tumor cells. In the last two decades, EBV-specific cytotoxic T-lymphocytes (CTL) have been successfully employed for the prophylaxis and treatment of EBV-related lymphoproliferative disorders in immunocompromised hosts. More recently, this therapeutic approach has been applied to the setting of EBV-related solid tumors, such as nasopharyngeal carcinoma. The results are encouraging, although further improvements to the clinical protocols are clearly necessary to increase anti-tumor activity. Promising implementations are underway, including harnessing the therapeutic potential of CTLs specific for subdominant EBV latent cycle epitopes, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells

High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis

Rheumatoid and psoriatic arthritis (RA and PsA) are inflammatory rheumatic disorders characterised by a multifactorial etiology. To date, the genetic contributions to the disease onset, severity and drug response are not clearly defined, and despite the development of novel targeted therapies, ~10% of patients still display poor treatment responses. We characterised a selected cohort of eleven non-responder patients aiming to define the genetic contribution to drug resistance. An accurate clinical examination of the patients was coupled with several high-throughput genetic testing, including HLA typing, SNPs-array and Whole Exome Sequencing (WES). The analyses revealed that all the subjects carry very rare HLA phenotypes which contain HLA alleles associated with RA development (e.g., HLA-DRB1*04, DRB1*10:01 and DRB1*01). Additionally, six patients also carry PsA risk alleles (e.g., HLA-B*27:02 and B*38:01). WES analysis and SNPs-array revealed 23 damaging variants with 18 novel “drug-resistance” RA/PsA candidate genes. Eight patients carry likely pathogenic variants within common genes (CYP21A2, DVL1, PRKDC, ORAI1, UGT2B17, MSR1). Furthermore, “private” damaging variants were identified within 12 additional genes (WNT10A, ABCB7, SERPING1, GNRHR, NCAPD3, CLCF1, HACE1, NCAPD2, ESR1, SAMHD1, CYP27A1, CCDC88C). This multistep approach highlighted novel RA/PsA candidate genes and genotype-phenotype correlations potentially useful for clinicians in selecting the best therapeutic strategy

Radiomics and prostate MRI: Current role and future applications

Multiparametric prostate magnetic resonance imaging (mpMRI) is widely used as a triage test for men at a risk of prostate cancer. However, the traditional role of mpMRI was confined to prostate cancer staging. Radiomics is the quantitative extraction and analysis of minable data from medical images; it is emerging as a promising tool to detect and categorize prostate lesions. In this paper we review the role of radiomics applied to prostate mpMRI in detection and localization of prostate cancer, prediction of Gleason score and PI-RADS classification, prediction of extracapsular extension and of biochemical recurrence. We also provide a future perspective of artificial intelligence (machine learning and deep learning) applied to the field of prostate cancer

Role of molecular imaging in the management of patients affected by inflammatory bowel disease: State-of-the-art

To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease (IBD)