Case Report: A Peculiar Case of Inflammatory Colitis After SARS-CoV-2 Infection

open14noWe report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARSCoV- 2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/ PD-L1 interaction leading to early death of the patient.openRutigliani, Mariangela; Bozzo, Matteo; Barberis, Andrea; Greppi, Marco; Anelli, Emanuela; Castellaro, Luca; Bonsignore, Alessandro; Azzinnaro, Antonio; Pesce, Silvia; Filauro, Marco; Rollandi, Gian Andrea; Castagnola, Patrizio; Candiani, Simona; Marcenaro, EmanuelaRutigliani, Mariangela; Bozzo, Matteo; Barberis, Andrea; Greppi, Marco; Anelli, Emanuela; Castellaro, Luca; Bonsignore, Alessandro; Azzinnaro, Antonio; Pesce, Silvia; Filauro, Marco; Rollandi, Gian Andrea; Castagnola, Patrizio; Candiani, Simona; Marcenaro, Emanuel

Jerusalem. The holy sepulcher. Research and investigation

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The kinetics of 18F-FDG in lung cancer: compartmental models and voxel analysis

Abstract Background The validation of the most appropriate compartmental model that describes the kinetics of a specific tracer within a specific tissue is mandatory before estimating quantitative parameters, since the behaviour of a tracer can be different among organs and diseases, as well as between primary tumours and metastases. The aims of our study were to assess which compartmental model better describes the kinetics of 18F-Fluorodeoxygluxose(18F-FDG) in primary lung cancers and in metastatic lymph nodes; to evaluate whether quantitative parameters, estimated using different innovative technologies, are different between lung cancers and lymph nodes; and to evaluate the intra-tumour inhomogeneity. Results Twenty-one patients (7 females; 71 ± 9.4 years) with histologically proved lung cancer, prospectively evaluated, underwent 18F-FDG PET-CT for staging. Spectral analysis iterative filter (SAIF) method was used to design the most appropriate compartmental model. Among the compartmental models arranged using the number of compartments suggested by SAIF results, the best one was selected according to Akaike information criterion (AIC). Quantitative analysis was performed at the voxel level. K 1, V b and K i were estimated with three advanced methods: SAIF approach, Patlak analysis and the selected compartmental model. Pearson’s correlation and non-parametric tests were used for statistics. SAIF showed three possible irreversible compartmental models: Tr-1R, Tr-2R and Tr-3R. According to well-known 18F-FDG physiology, the structure of the compartmental models was supposed to be catenary. AIC indicated the Sokoloff’s compartmental model (3K) as the best one. Excellent correlation was found between K i estimated by Patlak and by SAIF (R 2 = 0.97, R 2 = 0.94, at the global and the voxel level respectively), and between K i estimated by 3K and by SAIF (R 2 = 0.98, R 2 = 0.95, at the global and the voxel level respectively). Using the 3K model, the lymph nodes showed higher mean and standard deviation of V b than lung cancers (p < 0.0014, p < 0.0001 respectively) and higher standard deviation of K 1 (p < 0.005). Conclusions One-tissue reversible plus one-tissue irreversible compartmental model better describes the kinetics of 18F-FDG in lung cancers, metastatic lymph nodes and normal lung tissues. Quantitative parameters, estimated at the voxel level applying different advanced approaches, show the inhomogeneity of neoplastic tissues. Differences in metabolic activity and in vascularization, highlighted among all cancers and within each individual cancer, confirm the wide variability in lung cancers and metastatic lymph nodes. These findings support the need of a personalization of therapeutic approaches

Epilepsy in multiple sclerosis: The role of temporal lobe damage

Background: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. Objectives: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. Methods: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Results: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS (p< 0.05 for all comparisons). Conclusions: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed

Epilepsy in multiple sclerosis: The role of temporal lobe damage

BACKGROUND: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. OBJECTIVES:To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis.METHODS:A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model.RESULTS:Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS (p< 0.05 for all comparisons).CONCLUSIONS:Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed