The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Fabrication of a three-dimensional optical vortices phase mask for astronomy by means of electron-beam lithography

In this work, a novel three-dimensional (3D) fabrication process was used to create a series of particular phase masks for astronomical applications. These phase masks, also known as spiral phase plates (SPP), find their application in astronomy for optical vortex coronagraphy in the search of extra solar planets. The 3D profile was directly written on 2.7 mm thick polymethylmethacrylate (PMMA) slide by electron beam lithography (EBL). The effect of electron scattering on topography profile was investigated and the relationship among spatial distribution of electron beam irradiation, spot size and dosage level of irradiation were experimentally characterized. The quality of the fabricated profiles was evaluated using atomic force microscopy (AFM) technique. SPPs were then optically tested by injecting a Gaussian beam and an airy diffraction pattern obtained from a laser source comparing the optical vortices so far obtained with those drawn with numerical simulations. (C) 2008 Elsevier B.V. All rights reserved

Analysis of Prognostic Factors for Resected Synchronous and Metachronous Liver Metastases from Colorectal Cancer

Background. Surgical treatment is the cornerstone in the management of colorectal cancer (CRC) liver metastases. The aim of this study is to identify clinicopathological factors affecting disease-free (DFS) and overall survival (OS) in patients undergoing potentially curative liver resection for CRC metastasis. Methods. All consecutive patients undergoing liver resection for first recurrence of CRC from February 2006 to February 2018 were included. Prognostic impact of factors related to the patient, primary and metastatic tumors, was retrospectively tested through univariate and multivariate analyses. Results. Seventy patients were included in the study. Median postoperative follow-up was 37 months (range 1–119). Median DFS and OS were 15.2 and 62.7 months, and 5-year DFS and OS rates were 16% and 53%. In univariate analysis, timing of metastasis presentation/treatment (combined colorectal and liver resection, “bowel first” approach or metachronous presentation) (p<0.0001), ASA score (p=0.003), chemotherapy after liver surgery (p=0.028), T stage (p=0.021), number of resected liver lesions (p<0.0001), and liver margin status (p=0.032) was significantly associated with DFS while peritoneal resection at colorectal surgery (p=0.026), ASA score (p=0.036), extension of liver resection (p=0.024), chemotherapy after liver surgery (p=0.047), and positive nodes (p=0.018) with OS. In multivariate analysis, timing of metastasis presentation/treatment, ASA score, and chemotherapy (before and after liver surgery) resulted significantly associated with DFS and timing of metastasis presentation/treatment, positive nodes, peritoneal resection at colorectal surgery, and surgical approach (open or minimally invasive) of colorectal resection with OS. Conclusions. Surgery may provide good DFS and OS rates for CRC liver metastasis. Patient selection for surgery and correct timing of intervention within a multidisciplinary approach may be improved by taking into account negative prognostic factors which stress the importance of systemic therapy

The Different Functional Distribution of “Not Effector” T Cells (Treg/Tnull) in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide, ranking as high as the second leading cause of cancer-related deaths in industrialized countries. Consistent with immunosurveillance theory, the immune system is crucial to protect the host from developing tumors, and the major players in tumoral immunity are effector T cells. Anyway, cancer cells develop strategies of immunoevasion influencing the cancer-specific lymphocyte priming, activation, and effector function. Therefore, the T cell subsets that mature during the stages of tumor growth, differently contribute to disease progression and/or regression. In our study, we analyzed the intra-tumoral and peripheral T cell subsets’ distribution in 30 patients with CRC, in order to clarify their functional role toward cancer. We found that percentage of infiltrating effector T cells decreased in cancer tissue than in healthy mucosa and that the tumor microenvironment negatively influences the cytolytic activity of T lymphocytes reactive to cancer cells. Moreover, we found that the tumor tissue was infiltrated by a large amount of “not effector” T (neT) cells with a regulatory or an anergic profile, which are unable to kill cancer cells, may be contributing to the CRC promotion. The presence of neT cells was investigated also in the peripheral blood of CRC patients, demonstrating that the peripheral T regulatory cells can inhibit the proliferation of effector T cells, confirming their immunosuppressive properties. Finally, monitoring the changes in circulating neT cells’ frequencies after the tumor removal, we confirmed the role of cancer in the modulation of immune system, in particular, in supporting a Tregs-mediated immunosuppression

Preliminary Comparison of Oral and Intestinal Human Microbiota in Patients with Colorectal Cancer: A Pilot Study

In this study Next-Generation Sequencing (NGS) was used to analyze and compare human microbiota from three different compartments, i.e., saliva, feces, and cancer tissue (CT), of a selected cohort of 10 Italian patients with colorectal cancer (CRC) vs. 10 healthy controls (saliva and feces). Furthermore, the Fusobacterium nucleatum abundance in the same body site was investigated through real-time quantitative polymerase chain reaction (qPCR) to assess the association with CRC. Differences in bacterial composition, F. nucleatum abundance in healthy controls vs. CRC patients, and the association of F. nucleatum with clinical parameters were observed. Taxonomic analysis based on 16S rRNA gene, revealed the presence of three main bacterial phyla, which includes about 80% of reads: Firmicutes (39.18%), Bacteroidetes (30.36%), and Proteobacteria (10.65%). The results highlighted the presence of different bacterial compositions; in particular, the fecal samples of CRC patients seemed to be enriched with Bacteroidetes, whereas in the fecal samples of healthy controls Firmicutes were one of the major phyla detected though these differences were not statistically significant. The CT samples showed the highest alpha diversity values. These results emphasize a different taxonomic composition of feces from CRC compared to healthy controls. Despite the low number of samples included in the study, these results suggest the importance of microbiota in the CRC progression and could pave the way to the development of therapeutic interventions and novel microbial-related diagnostic tools in CRC patients