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Previous studies have shown that glial and neuronal changes may trigger synaptic dysfunction in Alzheimer's disease(AD). However, the link between glial and neuronal markers and synaptic abnormalities in the living brain is poorly understood. Here, we investigated the association between biomarkers of astrocyte and microglial reactivity and synaptic dysfunction in 478 individuals across the aging and AD spectrum from two cohorts with available CSF measures of amyloid-β(Aβ), phosphorylated tau(pTau181), astrocyte reactivity(GFAP), microglial activation(sTREM2), and synaptic biomarkers(GAP43 and neurogranin). Elevated CSF GFAP levels were linked to presynaptic and postsynaptic dysfunction, regardless of cognitive status or Aβ presence. CSF sTREM2 levels were associated with presynaptic biomarkers in cognitively unimpaired and impaired Aβ + individuals and postsynaptic biomarkers in cognitively impaired Aβ + individuals. Notably, CSF pTau181 levels mediated all associations between GFAP or sTREM2 levels and synaptic dysfunction biomarkers. These results suggest that neuronal-related synaptic biomarkers could be used in clinical trials targeting glial reactivity in AD.

Background & Aims: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours., Methods: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure., Results: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96)., Conclusions: Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumours), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes., Impact and Implications: Immune-related liver injury (irLI) is common in patients with cancer receiving immune checkpoint inhibitors (ICIs), but whether irLI is more frequent or it is associated with a worse clinical course in patients with hepatocellular carcinoma (HCC), compared to other tumours, is not known. Herein, we compared characteristics and outcomes of irLI in two prospective cohorts including patients treated with ICIs for HCC or for other oncological indications. irLI is significantly more common and it occurs earlier in patients with HCC, also after adjustment for duration of treatment exposure. However, outcomes of patients with HCC who developed irLI are not negatively affected in terms of requirement for corticosteroid therapy, hepatic decompensation, treatment discontinuation and overall survival., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration., Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR)., Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007)., Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity., Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus., Competing Interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study from Roche S.p.A. and Seqirus, and outside the present research from Astra Zeneca, Bristol-Myers Squibb (BMS), and Sanofi. MB received funding for the present study from Roche S.p.A. and Seqirus (through FICOG as Institution, no personal fees). She also received, outside the current work: research funding from Pfizer and Novartis (through Institutions); honoraria as a speaker at scientific events (personal fees) by BMS, MSD, IPSEN, Novartis, Astra Zeneca, Pierre Fabre, and Pfizer; as a consultant for advisory role (personal fees) by IPSEN, Novartis, Sanofi, Pierre-Fabre, and Merck; personal fees for copyright transfer by Sciclone Pharmaceuticals, Pierre-Fabre, MSD, IPSEN, Pfizer, and Sanofi. AC received speakers fees/grant consultancies from Astrazeneca, BMS, MSD, EISAI, IQVIA, and OncoC4. UDG has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study. MDM reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. SB received honoraria as a speaker at scientific events and in advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. VS participated, with personal fees, to advisory boards and speaker's bureaus for Roche S.p.A. SC declared his role in an international board for Eli Lilly international. AR declares Advisory Board activity for Bristol, Pfizer, Bayer, and Kyowa Kirin, and speaker honorarium from Roche Diagnostics. PAZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. MS received honoraria for advisory role from Janssen, and travel and accommodation expenses from Janssen, IPSEN, BMS, Astellas, and Pfizer. ER had a role as consultant for MSD, Novartis, Pierre Fabre, Immunocore and Pfizer. FG received personal fees from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, MSD, BMS, Pierre Fabre, Novartis, Merck, Takeda, Bayer, Novartis, and AMGEN for consulting activity; from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, BMS, AMGEN, MSD, Celgene, and Pierre Fabre for speakers bureaus. GG declares speaker and advisory fees from MSD; Travels and Accommodations from AstraZeneca. DaS declares honoraria for advisory board from Astellas, Janssen, Bayer, Novartis, Astra-Zeneca, MSD, BMS, Roche. FM received personal fees for advisory role by Roche, MSD, Takeda, Novartis, Sanofi. RRS received travel grants from AIOM and CIPOMO, and declares memberships in AIOM, CIPOMO, ESMO, ASCO and Rotary Club. SP received honoraria as a speaker from Roche, Astra Zeneca, MSD, and GSK. DG received honoraria as a speaker from Amgen. MR received honoraria as speaker/consultant by MSD, Astra Zeneca, Bristol-MyersSquibb (BMS), Novartis, and Pfizer. All the cited competing interests were outside the current work and not related to the content of our manuscript if not differently specified. All remaining authors have declared no conflicts of interest., (© 2023 The Authors.)

Objectives: To test reproducibility and predictive value of a simplified score for assessment of extraprostatic tumor extension (sEPE grade)., Methods: Sixty-five patients (mean age ± SD, 67 years ± 6.3) treated with radical prostatectomy for prostate cancer who underwent 1.5-Tesla multiparametric magnetic resonance imaging (mpMRI) 6 months before surgery were enrolled. sEPE grade was derived from mpMRI metrics: curvilinear contact length > 15 mm (CCL) and capsular bulging/irregularity. The diameter of the index lesion (dIL) was also measured. Evaluations were independently performed by seven radiologists, and inter-reader agreement was tested by weighted Cohen K coefficient. A nested (two levels) Monte Carlo cross-validation was used. The best cut-off value for dIL was selected by means of the Youden J index to classify values into a binary variable termed dIL*. Logistic regression models based on sEPE grade, dIL, and clinical scores were developed to predict pathologic EPE. Results on validation set were assessed by the main metrics of the receiver operating characteristics curve (ROC) and by decision curve analysis (DCA). Based on our findings, we defined and tested an alternative sEPE grade formulation., Results: Pathologic EPE was found in 31/65 (48%) patients. Average κ w was 0.65 (95% CI 0.51-0.79), 0.66 (95% CI 0.48-0.84), 0.67 (95% CI 0.50-0.84), and 0.43 (95% CI 0.22-0.63) for sEPE grading, CLL ≥ 15 mm, dIL*, and capsular bulging/irregularity, respectively. The highest diagnostic yield in predicting EPE was obtained by combining both sEPE grade and dIL*(ROC-AUC 0.81)., Conclusions: sEPE grade is reproducible and when combined with the dIL* accurately predicts extraprostatic tumor extension., Key Points: • Simple and reproducible mpMRI semi-quantitative scoring system for extraprostatic tumor extension. • sEPE grade accurately predicts extraprostatic tumor extension regardless of reader expertise. • Accurate pre-operative staging and risk stratification for optimized patient management., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Objective: Circular RNAs (circRNAs) are endogenous molecules of non-coding RNA that form a covalently closed loop at the 3' and 5' ends. Recently, the role of these molecules in the regulation of gene expression and their involvement in several human pathologies has gained notoriety. The identification of circRNAs is highly dependent on computational methods for analyzing RNA sequencing data. However, bioinformatics software is known to be problematic in terms of usability. Evidence points out that tools for identifying circRNAs can have such problems, negatively impacting researchers in this field. Here we present a heuristic-based framework for evaluating the usability of command-line circRNA identification software., Methods: We used heuristics evaluation to comprehensively identify the usability issues in a sample of circRNA identification tools., Results: We identified 46 usability issues presented individually in four tools. Most of the issues had cosmetic or minor severity. These are unlikely to challenge experienced users but may cause inconvenience for novice users. We also identified severe issues with the potential to harm users regardless of their experience. The areas most affected were the documentation and the installability of the tools., Conclusions: With the proposed framework, we formally describe, for the first time, the usability problems that can affect users in this area of circRNA research. We hope that our framework can help researchers evaluate their software's usability during development., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059−1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and “Bread and bakery” (p = 0.002), “salty convenience” (p = 0.005), and “sweet convenience” (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.

Mice homozygous for the nude mutation (Foxn1 nu ) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations., (Copyright © 2021. Published by Elsevier B.V.)

Background: Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence., Aim: To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences., Methods: We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021., Results: We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures., Conclusion: We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Autism spectrum disorder can present a plethora of clinical conditions associated with the disorder, such as greater brain volume in the first years of life in a significant percentage of patients. We aimed to evaluate the brain water content, the blood-brain barrier permeability, and the expression of aquaporin 1 and 4, and GFAP in a valproic acid-animal model, assessing the effect of resveratrol. On postnatal day 30, Wistar rats of the valproic acid group showed greater permeability of the blood-brain barrier to the Evans blue dye and a higher proportion of brain water volume, prevented both by resveratrol. Prenatal exposition to valproic acid diminished aquaporin 1 in the choroid plexus, in the primary somatosensory area, in the amygdala region, and in the medial prefrontal cortex, reduced aquaporin 4 in medial prefrontal cortex and increased aquaporin 4 levels in primary somatosensory area (with resveratrol prevention). Valproic acid exposition also increased the number of astrocytes and GFAP fluorescence in both primary somatosensory area and medial prefrontal cortex. In medial prefrontal cortex, resveratrol prevented the increased fluorescence. Finally, there was an effect of resveratrol per se on the number of astrocytes and GFAP fluorescence in the amygdala region and in the hippocampus. Thus, this work demonstrates significant changes in blood-brain barrier permeability, edema formation, distribution of aquaporin 1 and 4, in addition to astrocytes profile in the animal model of autism, as well as the use of resveratrol as a tool to investigate the mechanisms involved in the pathophysiology of autism spectrum disorder., (© 2021 International Society for Developmental Neuroscience.)

Background: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs)., Methods: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety., Results: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2)., Conclusion: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy., Competing Interests: Competing interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study by Seqirus and Roche S.p.A.; also received funding outside the present study by Astra Zeneca, Bristol-Myers Squibb (BMS), Sanofi.Melissa Bersanelli received funding for the present study by Seqirus and Roche S.p.A. (FICOG as Institution, no personal fees). She also received, outside the present work, research funding from Pfizer and Novartis (Institution); honoraria as a speaker at scientific events (personal fees) by Astra Zeneca, Bristol-Myers Squibb (BMS), Novartis and Pfizer; as consultant for advisory role (personal fees) by Novartis, BMS and Pfizer; for copyright transfer by Sciclone Pharmaceuticals.Ugo De Giorgi has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study.Massimo Di Maio reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca and Novartis; he also received research funding from Novartis.Vieri Scotti participated, with personal fees, to advisory boards and speaker’s bureaus for Roche S.p.A. Saverio Cinieri declared international board for Eli Lilly international. Paolo Andrea Zucali acts in a consultant or advisory role for Sanofi, BMS, Pfizer, MSD, Astellas, Janssen, Ipsen, Novartis, all outside the scope of work. Marcello Tiseo received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, and institutional research grants from Astra-Zeneca, Boehringer Ingelheim. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In Europe, the SARS-CoV-2 pandemic had its first epicenter in Italy. Despite a significant mortality rate, the severity of most cases of COVID-19 infection ranges from asymptomatic to mildly symptomatic, and silent infection affects a still-unknown proportion of the general population. No information is available on the prevalence and clinical impact of SARS-CoV-2 silent infection among patients with cancer receiving anticancer treatment during the pandemic., Materials and Methods: From April 1, 2020, to the end of the same month, 560 consecutive patients with cancer, asymptomatic for COVID-19 and on anticancer treatment at Papa Giovanni XXIII Hospital in Bergamo, were evaluated and tested for SARS-CoV-2. We implemented a two-step diagnostics, including the rapid serological immunoassay for anti-SARS-CoV-2 immunoglobulin (Ig) G/IgM and the nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test in case of seropositivity to identify SARS-CoV-2 silent carriers., Results: In 560 patients, 172 (31%) resulted positive for anti-SARS-CoV-2 IgM/IgG antibodies, regardless of different type of cancer, stage, and treatment. The Ig-seropositive patients were then tested with RT-PCR nasopharyngeal swabs, and 38% proved to be SARS-CoV-2 silent carriers. At an early follow-up, in the 97 SARS-CoV-2-seropositive/RT-PCR-negative patients who continued their anticancer therapies, only one developed symptomatic COVID-19 illness., Conclusion: Among patients with cancer, the two-step diagnostics is feasible and effective for SARS-CoV-2 silent carriers detection and might support optimal cancer treatment strategies at both the individual and the population level. The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in cases of RT-PCR-negative patients., Implications for Practice: This is the first study evaluating the prevalence and clinical impact of SARS-CoV-2 silent infection in actively treated patients with cancer, during the epidemic peak in one of the worst areas of the COVID-19 pandemic. Lacking national and international recommendations for the detection of asymptomatic SARS-CoV-2 infection, a pragmatic and effective two-step diagnostics was implemented to ascertain SARS-CoV-2 silent carriers. In this series, consisting of consecutive and unselected patients with cancer, the prevalence of both SARS-CoV-2-seropositive patients and silent carriers is substantial (31% and 10%, respectively). The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in case of RT-PCR-negative patients., (© 2020 AlphaMed Press.)

Background: In ambulatory patients with cancer with asymptomatic or pauci-symptomatic SARS-CoV-2 infection, the safety of targeted therapies (TTs), chemotherapy (CT) or immune checkpoint inhibitors (ICIs) therapy is still unknown., Material and Methods: From the start of the first epidemic wave of SARS-CoV-2 in Bergamo, Italy, we have prospectively screened all consecutive outpatients who presented for treatment to the Oncology Division of the Papa Giovanni XXIII Hospital, Bergamo for SARS-CoV-2 antigen expression. We identified patients treated with ICIs and compared these to patients with the same cancer subtypes treated with TTs or CT., Results: Between March 5 and May 18, 293 consecutive patients (49% melanoma, 34% non-small cell lung cancer, 9% renal cell carcinoma, 8% other) were included in this study: 159 (54%), 50 (17%) and 84 (29%) received ICIs, CT or TTs, respectively. Overall 89 patients (30.0%) were SARS-CoV-2 positive. Mortality of SARS-CoV-2-positive patients was statistically significantly higher compared with SARS-CoV-2 negative patients (8/89 vs 3/204, respectively, Fisher's exact test p=0.004). All deaths were due to COVID-19. Serious adverse events (SAEs) were more frequent in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative cases (Cochran-Mantel-Haenszel (CMH) test p=0.0008). The incidence of SAEs in SARS-CoV-2 positive compared with SARS-CoV-2 negative patients was similar in ICI and CT patients (17.3% and 3.7% for positive and negative patients in ICIs and 15.4% and 2.7% in CT, Breslow-Day test p=0.891). No COVID-19-related SAEs were observed in the TTs patients., Conclusions: The incidence of SAEs was higher for SARS-CoV-2-positive patients treated with ICIs and CT, mostly in advanced disease. No SAEs were observed in patients treated with TTs. SAEs were COVID-19 related rather than treatment related. Treatment with ICIs does not appear to significantly increase risk of SAEs compared with CT. This information should be considered when determining treatment options for patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)