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1. Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review

Author

Helena Buso, Claudia Discardi, Patrick Bez, Francesco Muscianisi, Jessica Ceccato, Cinzia Milito, Davide Firinu, Nicholas Landini, Mark G. Jones, Carla Felice, Marcello Rattazzi, Riccardo Scarpa, and Francesco Cinetto

Subjects
granulomatous disease, sarcoidosis, granulomatous lymphocytic interstitial lung disease, common variable immunodeficiency, Biology (General), QH301-705.5
Abstract

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.

Published
2024
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2. The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study

Author

Giulia Anna Maria Luigia Costanzo, Giuseppina Sanna, Francesco Pes, Carla Maria Deiana, Andrea Giovanni Ledda, Andrea Perra, Vanessa Palmas, Valeria Manca, Michela Miglianti, Ferdinando Coghe, Aldo Manzin, Stefano Del Giacco, Luchino Chessa, and Davide Firinu

Subjects
COVID–19, immune-mediated diseases, vaccine, interferon-gamma release assay, infections, Medicine
Abstract

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Published
2024
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3. Unraveling the Complexities of Mast Cells in Health and Disease

Author

Davide Firinu

Subjects
n/a, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

As we draw the curtain on this Special Issue dedicated to the intricate roles of mast cells (MCs) in health and disease, we reflect on the insights garnered from the array of research articles featured within the published papers of the International Journal of Molecular Sciences (IJMS) [...]

Published
2024
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4. The Stability of Social and Behavioral Rhythms and Unexpected Low Rate of Relevant Depressive Symptoms in Old Adults during the COVID-19 Pandemic

Author

Federica Sancassiani, Giulia Cossu, Elisa Cantone, Ferdinando Romano, Alessandra Perra, Antonio Urban, Samantha Pinna, Stefano Del Giacco, Roberto Littera, Davide Firinu, Luchino Chessa, Enzo Tramontano, Antonio Egidio Nardi, and Mauro Giovanni Carta

Subjects
COVID-19, pandemic, elderly, depression, circadian rhythms, social rhythms, Medicine
Abstract

Background: The disruption of social rhythms was found to be associated with depressive disorders during the COVID-19 pandemic; lower rates of these disorders were surprisingly found in old adults. The present study aims to verify the stability of social rhythms during lockdown in a sample of elderly people. Methods: Controlled cohort study (secondary analyses) of a previous randomized-controlled trial with the first evaluation in April 2019 (T0) and then 48 weeks later (T1) during the lockdown. The regulation of social and behavioral rhythms was measured through the Brief Social Rhythms Scale (BSRS); the Patient Health Questionnaire-9 (PHQ9) was adopted to detect relevant depressive symptoms. Results: 93 elderlies (73.36 ± 4.97 years old, 50.5% females) were evaluated at T0 and T1. Neither the total score of BSRS nor any of the 10 items showed a statistically significant difference comparing the two survey periods. The frequency of relevant depressive symptoms was 5.3% at T0 and 6.4% at T1 (OR = 0.8, CI95% 0.2–24). Conclusions: Among elderlies who did not show an increased risk of depression during the lockdown, social and behavioral rhythms remained exceptionally stable during the same period. Considering previous evidence about rhythms dysregulation preceding depression, their stability may be considered a factor of resilience.

Published
2024
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5. COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation

Author

Giada Sambugaro, Elena Brambilla, Giulia Costanzo, Vera Bonato, Andrea Giovanni Ledda, Stefano Del Giacco, Riccardo Scarpa, Marcello Rattazzi, Elisabetta Favero, Francesco Cinetto, and Davide Firinu

Subjects
COVID-19, type 2 inflammation, biologicals, asthma, Science
Abstract

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient’s vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

Published
2024
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7. Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022

Author

Cinzia Milito, Federica Pulvirenti, Giulia Garzi, Eleonora Sculco, Francesco Cinetto, Davide Firinu, Gianluca Lagnese, Alessandra Punziano, Claudia Discardi, Giulia Costanzo, Carla Felice, Giuseppe Spadaro, Simona Ferrari, and Isabella Quinti

Subjects
gastric cancer, common variable immunodeficiency, mortality, endoscopy, screening, Helicobacter pylori, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionIn patients with Common Variable Immunodeficiency, malignancy has been reported as the leading cause of death in adults, with a high risk of B-cell lymphomas and gastric cancer.MethodsWe conducted a five-year prospective study aiming to update the incidence and mortality of gastric cancer and the incidence of gastric precancerous lesions in 512 CVID patients who underwent a total of 400 upper gastrointestinal endoscopies.ResultsIn the pre-pandemic period, 0.58 endoscopies were performed per patient/year and in the COVID-19 period, 0.39 endoscopies were performed per patient/year. Histology revealed areas with precancerous lesions in about a third of patients. Patients who had more than one gastroscopy during the study period were more likely to have precancerous lesions. Two patients received a diagnosis of gastric cancer in the absence of Helicobacter pylori infection. The overall prevalence of Helicobacter pylori infection in biopsy specimens was 19.8% and related only to active gastritis. Among patients who had repeated gastroscopies, about 20% progressed to precancerous lesions, mostly independent of Helicobacter pylori.DiscussionWhile gastric cancer accounted for one in five deaths from CVID in our previous survey, no gastric cancer deaths were recorded in the past five years, likely consistent with the decline in stomach cancer mortality observed in the general population. However, during the COVID-19 pandemic, cancer screening has been delayed. Whether such a delay or true decline could be the reason for the lack of gastric cancer detection seen in CVID may become clear in the coming years. Due to the high incidence of precancerous lesions, we cannot rely on observed and predicted trends in gastric cancer mortality and strongly recommend tailored surveillance programs.

Published
2023
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8. Cofactors, age at onset, allergic comorbidities and gender are different in patients sensitized to omega-5 gliadin and Pru p 3

Author

Giulia Costanzo, Annalisa Matolo, Laura Saderi, Maria Rita Messina, Davide Firinu, Maria Pina Barca, Paolo Serra, Nicoletta Corso, Giovanni Sotgiu, and Stefano Del Giacco

Subjects
Medicine, Science
Abstract

Abstract Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin. We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between patients LTPs+ and Tri a 19+ that showed in the latter group a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure. Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies.

Published
2022
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9. A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

Author

Stefano Mocci, Roberto Littera, Luchino Chessa, Marcello Campagna, Maurizio Melis, Carla Maria Ottelio, Ignazio S. Piras, Sara Lai, Davide Firinu, Stefania Tranquilli, Alessia Mascia, Monica Vacca, Daniele Schirru, Luigi Isaia Lecca, Stefania Rassu, Federica Cannas, Celeste Sanna, Mauro Giovanni Carta, Francesca Sedda, Erika Giuressi, Selene Cipri, Michela Miglianti, Andrea Perra, and Sabrina Giglio

Subjects
COVID-19, Sardinian population, soluble HLA-G, HLA-G 3’UTR haplotypes, KIR2DS2 gene, neanderthal LZTFL1 variants, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionA large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection.Materials and MethodsWe compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy).ResultsHLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 – 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3’UTR polymorphism (rs371194629) shows that the HLA-G 3’UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3’UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 – 0.7), PM = 6.5 x 10-4].ConclusionOur results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

Published
2023
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10. The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA)

Author

Mauro Cancian, Paola Triggianese, Stella Modica, Francesco Arcoleo, Donatella Bignardi, Luisa Brussino, Caterina Colangelo, Ester Di Agosta, Davide Firinu, Maria Domenica Guarino, Francesco Giardino, Marica Giliberti, Vincenzo Montinaro, and Riccardo Senter

Subjects
C1-inhibitor (C1INH), contact system, rare disease, hereditary angioedema (HAE), pediatric, puberty, Pediatrics, RJ1-570
Abstract

IntroductionHereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks.MethodsRetrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA).ResultsThe proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p

Published
2023
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11. Multimodal, open-source big data analysis in asthma: A novel approach to inform public health programming

Author

Sebastiano Gangemi, MD, PhD, Alessandro Tonacci, PhD, Giulia Costanzo, MD, Davide Firinu, MD, and Stefano Del Giacco, MD, PhD

Subjects
Asthma, Big data, Socio economic status, Health programming, Epidemiology, Real data, Immunologic diseases. Allergy, RC581-607
Abstract

Asthma is a chronic respiratory disease affecting over 358 million people worldwide; for this reason analysing big data on asthma from different countries could give a more detailed picture of current disease burden. We aim to investigate the correlations between asthma and key socio-demographic parameters from different world databases. We found a direct correlation with the gross domestic product (GDP) per capita and its nominal counterpart, with wealthiest countries seen to have the highest prevalence of asthma, as also confirmed by a similar correlation with the human development index (HDI). A positive correlation was also seen between asthma prevalence and a number of socio-cultural data being representative of a good life quality index and prevalent in more developed and wealthier countries. Concerning medical data, an inverse relationship was seen between asthma prevalence and helminthiasis. Those data indicate a higher prevalence for asthma in more developed countries, where socio-economic status is higher and also the access to medical care is more ubiquitous. The approach used in our study highlighted the role of medical literacy and access to healthcare facilities in the correct diagnosis of asthma and vice versa. Our data appear to be suitable in terms of a health programming approach because of the high burden of disease worldwide.

Published
2023
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12. A beacon in the dark: COVID-19 course in CVID patients from two European countries: Different approaches, similar outcomes

Author

Cinzia Milito, Davide Firinu, Patrick Bez, Annalisa Villa, Alessandra Punziano, Gianluca Lagnese, Giulia Costanzo, Leanne P. M. van Leeuwen, Beatrice Piazza, Carla Maria Deiana, Giancarlo d’Ippolito, Stefano Renato Del Giacco, Marcello Rattazzi, Giuseppe Spadaro, Isabella Quinti, Riccardo Scarpa, Virgil A. S. H. Dalm, and Francesco Cinetto

Subjects
Common Variable Immunodeficiency (CVID), COVID-19, SARS-CoV-2, precision medicine, outpatient, risk factors, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundCVID patients present an increased risk of prolonged SARS-CoV-2 infection and re-infection and a higher COVID-19-related morbidity and mortality compared to the general population. Since 2021, different therapeutic and prophylactic strategies have been employed in vulnerable groups (vaccination, SARS-CoV-2 monoclonal antibodies and antivirals). The impact of treatments over the last 2 years has not been explored in international studies considering the emergence of viral variants and different management between countries.MethodsA multicenter retrospective/prospective real-life study comparing the prevalence and outcomes of SARS-CoV-2 infection between a CVID cohort from four Italian Centers (IT-C) and one cohort from the Netherlands (NL-C), recruiting 773 patients.Results329 of 773 CVID patients were found positive for SARS-CoV-2 infection between March 1st, 2020 and September 1st 2022. The proportion of CVID patients infected was comparable in both national sub-cohorts. During all waves, chronic lung disease, “complicated” phenotype, chronic immunosuppressive treatment and cardiovascular comorbidities impacted on hospitalization, whereas risk factors for mortality were older age, chronic lung disease, and bacterial superinfections. IT-C patients were significantly more often treated, both with antivirals and mAbs, than NL-C patients. Outpatient treatment, available only in Italy, started from the Delta wave. Despite this, no significant difference was found for COVID-19 severity between the two cohorts. However, pooling together specific SARS-CoV-2 outpatient treatments (mAbs and antivirals), we found a significant effect on the risk of hospitalization starting from Delta wave. Vaccination with ≥ 3 doses shortened RT-PCR positivity, with an additional effect only in patients receiving antivirals.ConclusionsThe two sub-cohorts had similar COVID-19 outcomes despite different treatment approaches. This points out that specific treatment should now be reserved for selected subgroups of CVID patients, based on pre-existing conditions.

Published
2023
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13. Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Author

Simone Serrao, Cristina Contini, Giulia Guadalupi, Alessandra Olianas, Greca Lai, Irene Messana, Massimo Castagnola, Giulia Costanzo, Davide Firinu, Stefano Del Giacco, Barbara Manconi, and Tiziana Cabras

Subjects
mastocytosis, cystatin D, protein interactions, human saliva, mass spectrometry, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Mastocytosis, a rare blood disorder characterized by the proliferation of clonal abnormal mast cells, has a variegated clinical spectrum and diagnosis is often difficult and delayed. Recently we proposed the cathepsin inhibitor cystatin D-R26 as a salivary candidate biomarker of systemic mastocytosis (SM). Its C26 variant is able to form multiprotein complexes (mPCs) and since protein–protein interactions (PPIs) are crucial for studying disease pathogenesis, potential markers, and therapeutic targets, we aimed to define the protein composition of the salivary cystatin D-C26 interactome associated with SM. An exploratory affinity purification-mass spectrometry method was applied on pooled salivary samples from SM patients, SM patient subgroups with and without cutaneous symptoms (SM+C and SM−C), and healthy controls (Ctrls). Interactors specifically detected in Ctrls were found to be implicated in networks associated with cell and tissue homeostasis, innate system, endopeptidase regulation, and antimicrobial protection. Interactors distinctive of SM−C patients participate to PPI networks related to glucose metabolism, protein S-nitrosylation, antibacterial humoral response, and neutrophil degranulation, while interactors specific to SM+C were mainly associated with epithelial and keratinocyte differentiation, cytoskeleton rearrangement, and immune response pathways. Proteins sensitive to redox changes, as well as proteins with immunomodulatory properties and activating mast cells, were identified in patients; many of them were involved directly in cytoskeleton rearrangement, a process crucial for mast cell activation. Although preliminary, these results demonstrate that PPI alterations of the cystatin D-C26 interactome are associated with SM and provide a basis for future investigations based on quantitative proteomic analysis and immune validation.

Published
2023
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14. Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab

Author

Andrea Giovanni Ledda, Giulia Costanzo, Giada Sambugaro, Cristiano Caruso, Martina Bullita, Maria Luisa Di Martino, Paolo Serra, Davide Firinu, and Stefano Del Giacco

Subjects
asthma, nasal polyps, eosinophils cationic protein, dupilumab, biomarkers, type 2 inflammation, Science
Abstract

Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Published
2023
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15. HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections

Author

Eleonora Loi, Loredana Moi, Paola Cabras, Giulia Arduino, Giulia Costanzo, Stefano Del Giacco, Henry A. Erlich, Davide Firinu, Aldo Caddori, and Patrizia Zavattari

Subjects
COVID-19, SARS-CoV-2, DNA methylation, HLA-C, gene expression, enhancer transcriptional regulation, Immunologic diseases. Allergy, RC581-607
Abstract

One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host’s immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response.

Published
2022
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16. The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis

Author

Roberto Littera, Andrea Perra, Michela Miglianti, Ignazio S. Piras, Stefano Mocci, Sara Lai, Maurizio Melis, Teresa Zolfino, Cinzia Balestrieri, Maria Conti, Giancarlo Serra, Francesco Figorilli, Davide Firinu, Simona Onali, Laura Matta, Carmen Porcu, Francesco Pes, Daniela Fanni, Cristina Manieli, Monica Vacca, Roberto Cusano, Marcello Trucas, Selene Cipri, Stefania Tranquilli, Stefania Rassu, Federica Cannas, Mauro Giovanni Carta, Marta Anna Kowalik, Erika Giuressi, Gavino Faa, Luchino Chessa, and Sabrina Giglio

Subjects
type 1 autoimmune hepatitis, Sardinian population, human leukocyte antigen, HLA-G alleles, soluble HLA-G, plasma cell, Immunologic diseases. Allergy, RC581-607
Abstract

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH).Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy).ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D’ = 0.92 vs D’ = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 – 17.4) U/mL vs 21.3 (16.5 – 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 – 44.8) U/mL vs 8.8 (6.1 – 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies.ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.

Published
2022
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17. Struggling with COVID-19 in Adult Inborn Errors of Immunity Patients: A Case Series of Combination Therapy and Multiple Lines of Therapy for Selected Patients

Author

Patrick Bez, Giancarlo D’ippolito, Carla Maria Deiana, Renato Finco Gambier, Andrea Pica, Giulia Costanzo, Giulia Garzi, Riccardo Scarpa, Nicholas Landini, Francesco Cinetto, Davide Firinu, and Cinzia Milito

Subjects
COVID-19, SARS-CoV-2, IEIs, antivirals, monoclonal antibodies, CVID, Science
Abstract

Background: The SARS-CoV-2 infection is now a part of the everyday lives of immunocompromised patients, but the choice of treatment and the time of viral clearance can often be complex, exposing patients to possible complications. The role of the available antiviral and monoclonal therapies is a matter of debate, as are their effectiveness and potential related adverse effects. To date, in the literature, the amount of data on the use of combination therapies and on the multiple lines of anti-SARS-CoV-2 therapy available to the general population and especially to inborn error of immunity (IEI) patients is small. Methods: Here, we report a case series of five adult IEI patients managed as inpatients at three Italian IEI referral centers (Rome, Treviso, and Cagliari) treated with combination therapy or multiple therapeutic lines for SARS-CoV-2 infection, such as monoclonal antibodies (mAbs), antivirals, convalescent plasma (CP), mAbs plus antiviral, and CP combined with antiviral. Results: This study may support the use of combination therapy against SARS-CoV-2 in complicated IEI patients with predominant antibody deficiency and impaired vaccine response.

Published
2023
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18. Right Ventricular Subclinical Dysfunction in SLE Patients Correlates with Metabolomic Fingerprint and Organ Damage

Author

Martino Deidda, Antonio Noto, Davide Firinu, Cristina Piras, William Cordeddu, Claudia Depau, Giulia Costanzo, Stefano Del Giacco, Luigi Atzori, Giuseppe Mercuro, and Christian Cadeddu Dessalvi

Subjects
metabolomics, 3D echocardiography, global longitudinal strain, systemic lupus erythematosus, Microbiology, QR1-502
Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC). In addition, a metabolomic analysis was performed. Direct correlations were observed between TAPSE values and the RV 3D parameters. Then, when splitting the population according to the SDI value, it was found that patients with higher cumulative damage (≥3) had significantly lower FAC, RV-EF, Septal LS, and Free-LS values; the latter three parameters showed a significant correlation with the metabolic profile of the patients. Furthermore, the division based on SDI values identified different metabolic profiles related to the degree of RV dysfunction. The RV dysfunction induced by the chronic inflammatory state present in SLE can be identified early by 3D echocardiography. Its severity seems to be related to systemic organ damage and the results associated with a specific metabolic fingerprint constituted by 2,4-dihydroxybutyric acid, 3,4-dihydroxybutyric acid, citric acid, glucose, glutamine, glycine, linoleic acid, oleic acid, phosphate, urea, and valine.

Published
2023
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19. Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic

Author

Giulia Garzi, Francesco Cinetto, Davide Firinu, Giulia Di Napoli, Gianluca Lagnese, Alessandra Punziano, Patrick Bez, Bianca Laura Cinicola, Giulia Costanzo, Riccardo Scarpa, Federica Pulvirenti, Marcello Rattazzi, Giuseppe Spadaro, Isabella Quinti, and Cinzia Milito

Subjects
inborn errors of immunity, COVID-19, monoclonal antibodies, antiviral drugs, hospitalization-risk, disease severity, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundSince the beginning of the COVID-19 pandemic, patients with Inborn Errors of Immunity have been infected by SARS-CoV-2 virus showing a spectrum of disease ranging from asymptomatic to severe COVID-19. A fair number of patients did not respond adequately to SARS-CoV-2 vaccinations, thus early therapeutic or prophylactic measures were needed to prevent severe or fatal course or COVID-19 and to reduce the burden of hospitalizations.MethodsLongitudinal, multicentric study on patients with Inborn Errors of Immunity immunized with mRNA vaccines treated with monoclonal antibodies and/or antiviral agents at the first infection and at reinfection by SARS-CoV-2. Analyses of efficacy were performed according to the different circulating SARS-CoV-2 strains.ResultsThe analysis of the cohort of 192 SARS-CoV-2 infected patients, across 26 months, showed the efficacy of antivirals on the risk of hospitalization, while mabs offered a positive effect on hospitalization, and COVID-19 severity. This protection was consistent across the alpha, delta and early omicron waves, although the emergence of BA.2 reduced the effect of available mabs. Hospitalized patients treated with mabs and antivirals had a lower risk of ICU admission. We reported 16 re-infections with a length of SARS-CoV-2 positivity at second infection shorter among patients treated with mabs. Treatment with antivirals and mabs was safe.ConclusionsThe widespread use of specific therapy, vaccination and better access to care might have contributed to mitigate risk of mortality, hospital admission, and severe disease. However, the rapid spread of new viral strains underlines that mabs and antiviral beneficial effects should be re- evaluated over time.

Published
2022
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20. Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA)

Author

Roberta Parente, Silvio Sartorio, Luisa Brussino, Tiziana De Pasquale, Alessandra Zoli, Stefano Agolini, Ester Di Agosta, Paolina Quattrocchi, Paolo Borrelli, Donatella Bignardi, Angelica Petraroli, Riccardo Senter, Valentina Popescu Janu, Chiara Cogliati, Maria Domenica Guarino, Oliviero Rossi, Davide Firinu, Stefano Pucci, Giuseppe Spadaro, Massimo Triggiani, Mauro Cancian, and Andrea Zanichelli

Subjects
hereditary angioedema, acquired angioedema, C1 inhibitor, COVID-19, SARS-CoV-2, vaccination, Medicine
Abstract

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.

Published
2023
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21. A Protective HLA Extended Haplotype Outweighs the Major COVID-19 Risk Factor Inherited From Neanderthals in the Sardinian Population

Author

Stefano Mocci, Roberto Littera, Stefania Tranquilli, Aldesia Provenzano, Alessia Mascia, Federica Cannas, Sara Lai, Erika Giuressi, Luchino Chessa, Goffredo Angioni, Marcello Campagna, Davide Firinu, Maria Del Zompo, Giorgio La Nasa, Andrea Perra, and Sabrina Giglio

Subjects
COVID-19, SARS-CoV-2, Neanderthal Covid-19 risk haplotype, rs35044562 variant, HLA-A*02:01, B*18:01, Immunologic diseases. Allergy, RC581-607
Abstract

Sardinia has one of the lowest incidences of hospitalization and related mortality in Europe and yet a very high frequency of the Neanderthal risk locus variant on chromosome 3 (rs35044562), considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 SARS-CoV-2 patients and 314 healthy Sardinian controls. One hundred and twenty patients were asymptomatic, 90 were pauci-symptomatic, 108 presented a moderate disease course and 40 were severely ill. All patients were analyzed for the Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness. The β°39 C>T Thalassemia variant (rs11549407), HLA haplotypes, KIR genes, KIRs and their HLA class I ligand combinations were also investigated. Our findings revealed an increased risk for severe disease in Sardinian patients carrying the rs35044562 high risk variant [OR 5.32 (95% CI 2.53 - 12.01), p = 0.000]. Conversely, the protective effect of the HLA-A*02:01, B*18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 – 41.0), p < 0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.

Published
2022
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22. Previous functional social and behavioral rhythms affect resilience to COVID-19-related stress among old adults

Author

Mauro Giovanni Carta, Michele Fornaro, Luigi Minerba, Massimiliano Pau, Fernanda Velluzzi, Laura Atzori, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera, Luchino Chessa, Davide Firinu, Stefano Del Giacco, Angelo Restivo, Simona Deidda, Germano Orrù, Alessandra Scano, Simona Onali, Ferdinando Coghe, Goce Kalcev, and Giulia Cossu

Subjects
Social and behavioral rhythms, Major Depressive Disorder, Health-Related Quality of Life, Covid-19, Resilience, Public aspects of medicine, RA1-1270
Abstract

Background: Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report. Design and methods: Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (³65 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) at week-48 (follow-up endpoint) were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS). Results: Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score at week-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI: 1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias. Conclusions: Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Published
2022
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23. Covid-19 vaccines work but other factors play a relevant role: a data analysis on spread and mortality in 24 countries

Author

Mauro Giovanni Carta, Germano Orrù, Giulia Cossu, Fernanda Velluzzi, Laura Atzori, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera, Luchino Chessa, Davide Firinu, Stefano Del Giacco, Angelo Restivo, Simona Deidda, Alessandra Scano, Simona Onali, Goce Kalcev, Ferinando Coghe, and Luigi Minerba

Subjects
Covid-19 vaccines, spread and mortality, countries, Public aspects of medicine, RA1-1270
Abstract

Background: The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing at two different times within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted. Design and methods: The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitants on 10 January 2021 (before vaccinations’ distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries). Results: The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role. Conclusions: This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

Published
2022
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24. COVID-19 Vaccine Hesitancy among Italian Healthcare Workers: Latent Profiles and Their Relationships to Predictors and Outcome

Author

Igor Portoghese, Melinda Siddi, Luchino Chessa, Giulia Costanzo, Vanessa Garcia-Larsen, Andrea Perra, Roberto Littera, Giada Sambugaro, Stefano Del Giacco, Marcello Campagna, and Davide Firinu

Subjects
vaccine hesitancy, latent profiles, healthcare workers, conspiracy beliefs, COVID-19, Medicine
Abstract

Vaccine hesitancy and conspiracy beliefs among healthcare workers (HCWs) represent operational priorities that require urgent attention. Identifying and classifying specific subpopulation of hesitancy is crucial to customize educational and intervention strategies to enhance the acceptance and uptake rate of vaccination. Thus, the main purpose of our study was to empirically identify latent profiles of vaccine hesitancy among Italian HCWs adopting a person-centered approach and investigating their relationships with antecedents and intention to get a fourth dose of COVID-19 vaccine. We conducted latent profile analyses (LPA) to identify different configurations of vaccine hesitancy based on five antecedents of vaccination: confidence, complacency, constraints, calculation, and collective responsibility among a sample of Italian HCWs (n = 573). LPA revealed four distinct profiles: believer (61.5%), middler (24.7%), hesitant (9.00%), and rejecter (4.7%). Having conspiracy beliefs was associated with a greater likelihood of membership in all but believer. Finally, the likelihood of intention to get a fourth dose of COVID-19 vaccine was lowest in the rejector and hesitant profiles. Theoretical contributions and implications for practice are discussed.

Published
2023
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26. Neutralizing Antibodies Responses against SARS-CoV-2 in a Sardinian Cohort Group Up to 9 Months after BNT162b2 Vaccination

Author

Giuseppina Sanna, Alessandra Marongiu, Davide Firinu, Cristina Piras, Gianluigi Franci, Massimiliano Galdiero, Giuseppe Pala, Vanessa Palmas, Fabrizio Angius, Roberto Littera, Andrea Perra, Germano Orrù, Marcello Campagna, Giulia Costanzo, Federico Meloni, Ferdinando Coghe, Luchino Chessa, and Aldo Manzin

Subjects
COVID-19, BNT162b2 vaccine, CLIA, Antibody, neutralization assay, Medicine
Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has caused over 460 million cases of infection and over 6 million deaths worldwide. The pandemic has called for science, technology, and innovation to provide solutions and, due to an incredible scientific and financial global effort, several prophylactic and therapeutic apparatuses such as monoclonal antibodies and vaccines were developed in less than one year to address this emergency. After SARS-CoV-2 infection, serum neutralizing antibodies are produced by B cells and studies on virus-neutralizing antibodies’ kinetics are pivotal. The process of protective immunity and the duration of this kind of protection against COVID-19 remain to be clarified. We tested 136 sera from 3 groups of individuals, some of them providing multiple sequential sera (1—healthy, no previous CoV2-infected, vaccinated; 2—healthy, previous CoV2 infected, vaccinated; 3—healed, previous CoV2-infected, not vaccinated) to assess the kinetics of antibodies (Abs) neutralizing activity. We found that SARS-CoV-2 infection elicits moderate neutralizing antibody activity in most individuals; neither age nor gender appear to have any influence on Abs responses. The BNT162b2 vaccine, when administered in two doses, induces high antibodies titre endowed with potent neutralizing activity against bare SARS-CoV-2 in in vitro neutralizing assay. The residual neutralization capability and the kinetic of waning immunity were also evaluated over 9 months after the second dose in a reference group of subjects. Neutralization titre showed a decline in all subjects and the median level of S-protein IgG, over 270 days after the second vaccination dose, was below 10 AU/mL in 53% of serum tested.

Published
2022
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27. Evaluation of Antibody Response to Heterologous Prime–Boost Vaccination with ChAdOx1 nCoV-19 and BNT162b2: An Observational Study

Author

Davide Firinu, Andrea Perra, Marcello Campagna, Roberto Littera, Federico Meloni, Francesca Sedda, Maria Conti, Giulia Costanzo, Monica Erbi, Gianmario Usai, Carlotta Locci, Mauro Giovanni Carta, Riccardo Cappai, Germano Orrù, Stefano Del Giacco, Ferdinando Coghe, and Luchino Chessa

Subjects
COVID-19, vaccination, immunogenicity, heterologous, ChAdOx1, BNT162b2, Medicine
Abstract

In several countries, thrombotic events after vaccination with ChAdOx1 nCoV-19 have led to heterologous messenger RNA (mRNA) boosting. We tested the antibody response to SARS-CoV-2 spike protein four weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/BNT), comparing data of homologous regimen (BNT/BNT, ChAd/ChAd) subjects positive for SARS-CoV-2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19. Methods: healthy subjects naïve for SARS-CoV-2 infection were assessed for serum IgG anti-S-RBD response 21 days after priming (T1), 4 (TFULL) and 15 (T15W) weeks after booster dose. Results: The median IgG anti-S-RBD levels at TFULL of Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S-RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescents were significantly lower than ChAd/BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S-RBD titer >75 AU/mL, correlated with high neutralizing titer, was 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescents. At T15W the titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S-RBD decline was reduced for ChAd/ChAd and similar for other combinations. Conclusion: Our data highlight the magnitude of IgG anti-S-RBD response in ChAd/BNT dosing, supporting the current national guidelines for heterologous boosting

Published
2021
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28. Eosinophilic Granulomatosis with Polyangiitis Relapse after COVID-19 Vaccination: A Case Report

Author

Giulia Costanzo, Andrea Giovanni Ledda, Alessandra Ghisu, Matteo Vacca, Davide Firinu, and Stefano Del Giacco

Subjects
EGPA, COVID-19, vaccine, mRNA BNT162b2 vaccine, relapse, Medicine
Abstract

Background: We here describe the case of a 71-year-old Caucasian woman previously diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA) that had been treated with Mepolizumab, an anti-IL5 monoclonal antibody, since 2019 with a good clinical response. Methods: She had a mild COVID-19 in December 2020 and she tested negative for SARS-CoV-2 infection in only late January 2021. In April 2021 she received the first dose of mRNA BNT162b2 vaccine. Ten days later she developed myalgia, dyspnea and numbness of the limbs due to a relapse of EGPA that occurred during Mepolizumab treatment.

Published
2021
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30. Different aspects of severe asthma in real life: Role of Staphylococcus aureus enterotoxins and correlation to comorbidities and disease severity

Author

Cristiano Caruso, Stefania Colantuono, Gabriele Ciasca, Umberto Basile, Riccardo Di Santo, Diego Bagnasco, Giovanni Passalacqua, Marco Caminati, Schiappoli Michele, Gianenrico Senna, Enrico Heffler, G. Walter Canonica, Nunzio Crimi, Rossella Intravaia, Eugenio De Corso, Davide Firinu, Antonio Gasbarrini, and Stefano R. Del Giacco

Subjects
biologicals, type 2 inflammation, Settore MED/12 - GASTROENTEROLOGIA, Immunology, Staphylococcus aureus enterotoxins, nasal polyposis, Immunology and Allergy, severe eosinophilic asthma
Abstract

Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non-invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP).The aim of this retrospective study was to evaluate the prevalence of SE-IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics.A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)-IgE positive. We found a meaningful association between SEB-IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB-IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB-IgE-positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB-IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB-IgE sensitization as an independent risk factor for developing asthma.Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.

Published
2022

31. Struggling with COVID-19 in Adult Inborn Errors of Immunity Patients: A Case Series of Combination Therapy and Multiple Lines of Therapy for Selected Patients

Author

Milito, Patrick Bez, Giancarlo D’ippolito, Carla Maria Deiana, Renato Finco Gambier, Andrea Pica, Giulia Costanzo, Giulia Garzi, Riccardo Scarpa, Nicholas Landini, Francesco Cinetto, Davide Firinu, and Cinzia

Subjects
COVID-19, SARS-CoV-2, IEIs, antivirals, monoclonal antibodies, CVID
Abstract

Background: The SARS-CoV-2 infection is now a part of the everyday lives of immunocompromised patients, but the choice of treatment and the time of viral clearance can often be complex, exposing patients to possible complications. The role of the available antiviral and monoclonal therapies is a matter of debate, as are their effectiveness and potential related adverse effects. To date, in the literature, the amount of data on the use of combination therapies and on the multiple lines of anti-SARS-CoV-2 therapy available to the general population and especially to inborn error of immunity (IEI) patients is small. Methods: Here, we report a case series of five adult IEI patients managed as inpatients at three Italian IEI referral centers (Rome, Treviso, and Cagliari) treated with combination therapy or multiple therapeutic lines for SARS-CoV-2 infection, such as monoclonal antibodies (mAbs), antivirals, convalescent plasma (CP), mAbs plus antiviral, and CP combined with antiviral. Results: This study may support the use of combination therapy against SARS-CoV-2 in complicated IEI patients with predominant antibody deficiency and impaired vaccine response.

Published
2023
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32. Right Ventricular Subclinical Dysfunction in SLE Patients Correlates with Metabolomic Fingerprint and Organ Damage

Author

Dessalvi, Martino Deidda, Antonio Noto, Davide Firinu, Cristina Piras, William Cordeddu, Claudia Depau, Giulia Costanzo, Stefano Del Giacco, Luigi Atzori, Giuseppe Mercuro, and Christian Cadeddu

Subjects
metabolomics, 3D echocardiography, global longitudinal strain, systemic lupus erythematosus
Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC). In addition, a metabolomic analysis was performed. Direct correlations were observed between TAPSE values and the RV 3D parameters. Then, when splitting the population according to the SDI value, it was found that patients with higher cumulative damage (≥3) had significantly lower FAC, RV-EF, Septal LS, and Free-LS values; the latter three parameters showed a significant correlation with the metabolic profile of the patients. Furthermore, the division based on SDI values identified different metabolic profiles related to the degree of RV dysfunction. The RV dysfunction induced by the chronic inflammatory state present in SLE can be identified early by 3D echocardiography. Its severity seems to be related to systemic organ damage and the results associated with a specific metabolic fingerprint constituted by 2,4-dihydroxybutyric acid, 3,4-dihydroxybutyric acid, citric acid, glucose, glutamine, glycine, linoleic acid, oleic acid, phosphate, urea, and valine.

Published
2023
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33. Multimodal, open-source big data analysis in asthma: A novel approach to inform public health programming()

Author

Sebastiano Gangemi, Alessandro Tonacci, Giulia Costanzo, Davide Firinu, and Stefano Del Giacco

Subjects
Pulmonary and Respiratory Medicine, Immunology, Correspondence, Immunology and Allergy
Abstract

Asthma is a chronic respiratory disease affecting over 358 million people worldwide; for this reason analysing big data on asthma from different countries could give a more detailed picture of current disease burden. We aim to investigate the correlations between asthma and key socio-demographic parameters from different world databases. We found a direct correlation with the gross domestic product (GDP) per capita and its nominal counterpart, with wealthiest countries seen to have the highest prevalence of asthma, as also confirmed by a similar correlation with the human development index (HDI). A positive correlation was also seen between asthma prevalence and a number of socio-cultural data being representative of a good life quality index and prevalent in more developed and wealthier countries. Concerning medical data, an inverse relationship was seen between asthma prevalence and helminthiasis. Those data indicate a higher prevalence for asthma in more developed countries, where socio-economic status is higher and also the access to medical care is more ubiquitous. The approach used in our study highlighted the role of medical literacy and access to healthcare facilities in the correct diagnosis of asthma and vice versa. Our data appear to be suitable in terms of a health programming approach because of the high burden of disease worldwide.

Published
2023

34. Successful Combination of Remdesivir and Convalescent Plasma to Treat a Patient with Rituximab-Related B-Cell Deficiency and Prolonged COVID-19: A Case Report

Author

Giorgio Raho, William Cordeddu, Davide Firinu, Stefano Del Giacco, and Goffredo Angioni

Subjects
Pharmacology, Infectious Diseases
Abstract

Background: Treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immuno-compromised patients with complete B cell depletion can be really challenging due to the lack of seroconversion and long-lasting disease. Case Report: We describe a case of long-lasting coronavirus disease (COVID-19) in a female patient with rheumatoid arthritis who was treated with rituximab and continued to show B-cell depletion. An ongoing replication of SARS-CoV-2 was demonstrated for a period of 8 months when nasopharyngeal swabs were tested. She was treated once with remdesivir but without lasting resolution, and she was then treated with convalescent plasma but with a similar effect. Only with a combination of both treatments was clinical resolution achieved. The patient's lack of seroconversion and the prolonged course of the disease illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case report highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission. Conclusions: The combination of remdesivir and convalescent plasma resulted in successfully achieving clinical resolution of SARS-CoV-2 infection in our patient.

Published
2023

35. The impact of cognitive impairment on Health-Related Quality of Life in Systemic Lupus Erythematosus: a cross-sectional study

Author

Giulia Costanzo, Lorena Lorefice, Davide Firinu, Elisa Carta, Giuseppe Murgia, Maria Rita Messina, Mario Torrazza, Carlotta Locci, Maria Pina Barca, Stefano Del Giacco, Eleonora Cocco, and Giuseppe Fenu

Abstract

Purpose: To correlate the cognitive functions evaluated by the Symbol Digit Modalities Test (SDMT)with the principal clinical features and Health-related Quality of Life (HRQoL) measures of SLE. Material and methods: We recruited consecutive outpatients with SLE from a third-level Lupus Clinic in Italy to undergo neuropsychological evaluation using SDMT and the LupusQoL-IT as HRQoL questionnaire. Patients were defined as either neuropsychiatric-SLE (NPSLE) or as non-neuropsychiatric-SLE (non-NPSLE); they were also classified as cognitive-impaired and cognitive-preserved based on SDMT score alteration corrected for age, gender and education. In this cross-sectional study we included and studied 140 consecutive patients; 30 patients had NPSLE. Inclusion criteria were 4 or more ACR criteria for SLE, exclusion criteria were non–italian speaking, ocular disease interfering with reading capacity, the onset of any major medical condition (e.g. requiring hospitalization) or overt new neuropsychiatric event within the study period. Results: The mean SDMT score was 41.4±12.8. Alteration of SDMT score was detected in 29.9% of patients. Pearson test showed a correlation between SDMT score and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR-SDI) score (r:-0.373, p< 0.001) and specific HRQoL domains. Cognitive-impaired and cognitive-preserved patients showed a significant difference in physical health (p=0.03), pain (p=0.04) and planning (p=0.02) domains of the HRQol. A multiple linear regression (dependent variable: SDMT score) revealed a relationship with SLICC/ACR-SDI (p=0.005) and with other clinical features, after adjustment. SDMT score was significantly more frequently altered among patients with NPSLE (p=0.009) and the mean was significantly different in comparison to non-NPSLE patients (p=0.01). Conclusions: Our data demonstrate the correlation between cognitive impairment captured using SDMT and HRQoL of SLE patients and show a correlation of measures such as SLICC/ACR-SDI with SDMT score.

Published
2023

36. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients

Author

Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators

Subjects
cardiovascular events, older patient, hypertension, antihypertensive drugs, older patients, survival, Clinical Biochemistry, antihypertensive drug, General Medicine, Biochemistry, cardiovascular event
Abstract

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Published
2023

37. Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

Author

Cinzia Milito, Francesco Cinetto, Giulia Garzi, Andrea Palladino, Marco Puca, Elena Brambilla, Camilla De Vitis, Giulia Costanzo, Riccardo Scarpa, Alessandra Punziano, Gianluca Lagnese, Stefano Del Giacco, Giuseppe Spadaro, Isabella Quinti, Davide Firinu, Milito, Cinzia, Cinetto, Francesco, Garzi, Giulia, Palladino, Andrea, Puca, Marco, Brambilla, Elena, De Vitis, Camilla, Costanzo, Giulia, Scarpa, Riccardo, Punziano, Alessandra, Lagnese, Gianluca, Del Giacco, Stefano, Spadaro, Giuseppe, Quinti, Isabella, and Firinu, Davide

Subjects
Vaccines, Immunology, CVID, adverse reaction, Immunology and Allergy, COVID-19, IEI patients, immunodeficiency, safety profile, IEI patient, Vaccine
Abstract

Purpose Little is known about vaccine safety in inborn errors of immunity (IEI) patients during the current vaccination campaign for COVID-19. To better investigate the reactogenicity and adverse event profile after two, three, and four doses of mRNA vaccines, we conducted an observational, multicentric study on 342 PID patients from four Italian Referral Centres. Methods We conducted a survey on self-reported adverse reactions in IEI patients who received mRNA vaccine by administering a questionnaire after each dose. Results Over the whole study period, none of the patients needed hospitalization or had hypersensitivity reactions, including anaphylaxis and delayed injection site reaction. After two vaccination doses, 35.4% of patients showed only local reactogenicity-related symptoms (RrS), 44.4% reported both systemic and local RrS, and 5% reported only systemic RrS. In more than 60% of cases, local or systemic RrS were mild. After the first and second booster doses, patients showed fewer adverse events (AEs) than after the first vaccination course. Patients aged 50 years and older reported adverse events and RrS less frequently. Among AEs requiring treatment, one common variable immune deficiency patient affected by T cell large granular lymphocytic leukemia developed neutropenia and one patient had Bell’s paralysis perhaps during herpes zoster reactivation. Conclusion Although our follow-up period is relatively short, the safety data we reported are reassuring. This data would help to contrast the vaccine hesitancy often manifested by patients with IEI and to better inform their healthcare providers.

Published
2023

38. Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Author

Crisafulli, Ernesto, Sartori, Giulia, Vianello, Alice, Busti, Fabiana, Nobili, Alessandro, Mannucci, Pier Mannuccio, Girelli, Domenico Investigators—Domenico Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene Mattioli (Azienda Ospedaliero Universitaria Careggi Firenze, SOD Medicina Interna Interdisciplinare), Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massi- miliano Chiuch (Azienda Sanitaria Universitaria Integrata di Trieste, Clinica Medica Generale, e Terapia Medica), Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi (Azienda Ospedaliera della Pro- vincia di Lecco, Ospedale di Merate, Lecco, Medicina, Interna), Matteo, Pirro, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Alessia, Giotta, Mannarino (Azienda Ospedaliera Santa Maria della Misericordia, Massimo R., Perugia, Medicina, Interna, Angiologia Malattie da Arteriosclerosi), Domenico, Girelli, Fabiana, Busti, Giacomo Marchi (Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Medicina Generale e Malattie Aterotrombotiche, e Degenerative), Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica Cacioppo (Azienda Ospedaliera Universitaria Policlinico Giaccone Policlinico di Palermo, Palermo, Unità Operativa di Geriatria, e Lun- godegenza), Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Civico, Federica Cavallaro (A. R. N. A. S., Cristina, Di, Benfratelli, Palermo, UOC Medicina Interna ad Indirizzo Geriatrico- Riabilitativo), Marco, Zoli, Maria Laura Mata- cena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Orsola-Malpighi, Angelo Simili (Azienda Ospe- daliera Universitaria Policlinico S., Bologna, Unità Operativa di Medicina Interna Zoli), Maria Domenica Cappellini, Gio- vanna Fabio, Margherita Migone De Amicis, Giacomo De Luca, Nata- lia Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta Mancarella (Fon- dazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Unità Operativa Medicina Interna IA), Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Federica, Conti, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Paola Nicolini (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Geriatria), Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra Cambiè (IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica Medica, I, Reparto, 11), Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico Cattaneo (IRCCS Azienda Ospedaliera Universitaria San Martino-IST di Genova, Gen-, Ova, Clinica di Medicina Interna 2), Luigi, Anastasio, Lucia, Sofia, Maria Carbone (Ospedale Civile Jazzolino di Vibo Valentia, Vibo Val- entia, Medicina, Generale), Francesco, Cipollone, Maria Teresa Guag- nano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D’Ardes, Lucia, Esposito, Simona, Sestili, Annunziata, Ermanno Angelucci (Ospedale Clinicizzato SS., Chieti, Clinica, Medica), Gerardo, Mancuso, Daniela, Calipari, Mosè Bartone (Ospedale Giovanni Paolo II Lamezia Terme, Catanzaro, Unità Operativa Complessa Medicina Interna), Giuseppe, Delitala, Maria, Berria, Alessandro Delitala (Azienda ospedaliera- universitaria di Sassari, Maurizio, Muscaritoli, Ales- sio Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Gio- vanni Imbimbo (Policlinico Umberto, I, Sapienza Università di Roma, Medicina Interna, e Nutrizione Clinica Policlinico Umberto I), Giuseppe, Zuccalà, Gemelli, Gabriella D’Aurizio (Policlinico Universitario A., Roma, Roma, Unità Operativa Complessa Medicina d'Urgenza, e Pronto Soccorso)Giuseppe Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto Zucchelli (Unità Operativa Complessa di Medicina I, a indirizzo geriatrico, Spedali, Civili, Montichiari, Brescia), Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara Dell’Unto (Università Campus Bio- Medico, Roma, Medicina Clinica-Epatolo- gia), Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Paolo, Mazzola, Andrea, Piazzoli, Gerardo, Maurizio Corsi (Università degli studi di Milano-Bicocca Ospedale S., Monza, Unità Operativa di Geri- atria), Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica Giofrè (Università degli Studi Magna Grecia, Policlinico Mater Domini, Cat-, Anzaro, Unità Operativa Complessa di Medicina Interna), Maria Grazia Serra, Maria Antonietta Bleve (Azienda Ospedaliera, Lecce, Unità Operativa Complessa Medicina), Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani (ASST FatebenefratelliSacco, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta Cosi (Azienda Ospe- daliera Università di Padova, Padova, Clinica Medica I), Roberto Man- fredini, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giulia Marta Viglione, Caterina Savriè (Azienda OspedalieraUniversitaria Sant'Anna, Ferrara, Unità Operativa Clinica Medica), Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo (Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, VI Divisione di Medicina Interna, e Malattie Nutrizionali dell'Invecchiamento), Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, 13 Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Orsola-Malpighi, Ilenia Pareo (Azienda Ospedaliera Universitaria Poli- clinico S., Unità Operativa di Medicina Interna Borghi), Carlo, Sabbà, Francesco Saverio Vella, Patrizia Sup- pressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Ema- nuele Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca Loparco (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Frugoni), Medicina Interna Universitaria C., Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore D’Aniano (Azienda Sanitaria Ospedaliera Santa Croce, e Carle di Cuneo, Cuneo, Ademe, Medicina Interna), S. C., Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice Cinque (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOC Medicina Generale ad Indirizzo Metabolico), Flora, Peyvandi, Raffaella, Rossio, Colombo, Giulia, Pasquale, Agosti, Erica, Pagliaro, Eleonora Semproni (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna, 2, Emato- logia non tumorale, e Coagulopatie), Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian Folli (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna Alta Intensità di Cure), Francesco, Salerno, Giada Pallini (IRCCS Policlinico San Donato, e Università di Milano, San Donato Milanese, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca Liberale (IRCCS Ospedale Policlinico San Martino, e Università di Genova, Genova, Clinica Medica, 1, Medicina Interna, e Specialità Mediche), Nicola Lucio Liberato, Tiziana Tognin (ASST di Pavia, UOSD Medicina Interna, Ospedale di Casorate Primo, Pavia), Francesco, Purrello, Antonino Di Pino, Salvatore Piro (Ospedale Garibaldi Nesima, Catania, Giorgia, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano Buf- felli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia Cesaroni (Ospedale Poliambulanza, Brescia, Medicina Interna, e Geriatria), Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura Sanino (Dipartimento di Scienze Mediche, Università di Torino, Città della Scienza, e della Salute, Torino, Medicina Interna, 2 Unità Indirizzo d'Urgenza), Franc- esco Violi, Ludovica Perri (Policlinico Umberto, I, Prima Clinica Medica), Guasti, Luigina, Rotunno, Francesca, Castiglioni, Luana, Maresca, ANDREA MARIA, Squizzato, Alessandro, Campiotti, Leonardo, Ales- sandra Grossi, Diprizio, ROBERTO DAVIDE, Francesco Dentali (Università degli Studi dell'Insubria, Ospedale di Circolo, e Fondazione Macchi, Varese, Elena, Medicina, e Geriatria), Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Elisa, Pellegrini, Laura, Orlandi, Giulia, Dondi, Lucia Carulli (Università di Modena, e Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Unità Operativa di Geriatria), Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco Filice, Elvira Clausi (Università Geriatriche), Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vec- chio, Ilaria Benzoni (Dipartimento di Scienze Mediche, e Chirurgiche, Unità Operativa di Medicina Interna, Orsola-Malpighi, Università degli Studi di Bologna/ Azienda Ospedaliero- Universitaria S., Bologna), Andrea, Salvi, Roberto, Leonardi, Giampaolo Damiani (Spedali Civili di Brescia, Medicina Generale), U. O. 3a., Gianluca, Moroncini, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto Romiti (Clinica Medica, Azienda Ospedaliera Universitaria- Ospedali Riuniti di Ancona), Riccardo, Ghio, Anna Dal Col (Azienda Ospedaliera Università San Martino, Medicina, III), Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo Labbadia (Poli- clinico Umberto, I, SMSC03Medicina Interna F, e Malattie Meta- boliche dell'osso), Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita (Policlinico Campus Biomedico Roma, Medicina, Clinica), Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Emanuele, Samuele Pignataro (Azienda Ospedaliera Universitaria Poli- clinico – V., Catania, Dipartimento di Medicina), Francesca, Mete, Miriam Gino (Ospedale degli Infermi di Rivoli, Medicina Interna)Guido Moreo, Gloria Pina (Clinica San Carlo Casa di Cura Polispecialistica, Paderno, Dugnano, Unità Operativa di Medicina Generale Emilio Bernardelli), Alberto Balle- strero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla Scarsi (Clinica Di Medicina Interna ad Indirizzo Oncologico, Azienda Ospedaliera Università San Martino di Genova), Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella Gruden (Medicina Interna III, Giovanni Battista Molinette, Ospedale S., Torino), Franco, Berti, Giuseppe, Famularo, Patrizia Tarsitani (Azienda Ospedaliera San Camillo Forlanini, Medicina Interna II), Roberto, Castello, Michela Pasino (Ospedale Civile Maggiore Borgo Trento, Medicina Generale, e Sezione di Decisione Cli- nica), Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta Mor- ganti, Andrea, Artoni, Margherita Grossi (Azienda Ospedaliero Uni- versitaria di Parma, Clinica Geriatrica), U. O. C., Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca Losa (Policlinico Universitario Duilio Casula, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Allergologia ed Immunologia Clinica), Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Angelo Rizzo (Azienda Ospe- daliera Universitaria Policlinico Paolo Giaccone, UOC di Medicina Interna), Francesco, Corica, Giorgio, Basile, Antonino Cata- lano, Federica, Bellone, Martino, Concetto Principato (Azienda Ospedaliera Universitaria Policlinico G., Messina, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella Caruso (Azienda Ospedaliera per l'Emergenza Cannizzaro, Clinica Medica Università di Catania), Patrizia, Mecocci, Carmelinda, Ruggiero, della Misericordia, Virginia Boccardi (Università degli Studi di Perugia-Azienda Ospedaliera S. M., Struttura Complessa di Geriatria), Tiziana, Meschi, Andrea, Ticinesi, Antonio Nouvenne (Azienda Ospedaliera Universitaria di Parma, Medicina Interna e Lungodegenza Critica), U. O., Pietro, Minuz, Luigi, Fondrieschi, Giandomen- ico Nigro Imperiale, Sarah Morellini (Azienda Ospedaliera Universi- taria Verona, Policlinico GB Rossi, Medicina Generale per lo Studio ed il Trattamento dell’Ipertensione Arteriosa), Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia Bellan (Azienda Ospedaliera Universitaria Maggiore della Carità, Medicina Interna 1), Roberto, Quadri, Erica, Larovere, Marco Novelli (Ospedale di Ciriè, Asl, To4, Emilio, Simeone, Rosa, Scurti, Fabio Tolloso (Ospedale Spirito Santo di Pescara, Geriatria), Roberto Tar- quini, Alice, Valoriani, Silvia, Dolenti, Giulia Vannini (Ospedale San Giuseppe, Empoli, USL Toscana Centro, Firenze, Medicina Interna I), Riccardo, Volpi, Pietro, Bocchi, Alessandro Vignali (Azienda Ospe- daliera Universitaria di Parma, Clinica, e Terapia Medica), Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia Aiello (Divisione di Medicina Interna, Multimedica, Ircss, Milano), Antonino Di Pino (Ospedale GaribaldiNesima, – Catania, Medicina Interna), U. O. C., Teresa, Salvatore, Lucio, Monaco, Vanvitelli, Carmen Ricozzi (Policlinico Università della Campania L., UOC Medicina Interna), Alberto, Pilotto, Ilaria, Indiano, Federica Gandolfo (Ente Ospe- daliero Ospedali Galliera Genova, SC Geriatria Dipartimento Cure Geriatriche, Ortogeriatria, e Riabilitazione)Franco Laghi Pasini, Pier Leopoldo Capecchi (Azienda Ospedaliera Universitaria Senese, Siena, Unità Operativa Complessa Medicina 2), Ranuccio, Nuti, Roberto Val- enti, Martina, Ruvio, Silvia, Cappelli, Alberto Palazzuoli (Azienda Ospedaliera Università Senese, Mauro Ber- nardi, Silvia Li Bassi, Luca, Santi, Giacomo Zaccherini (Azienda Ospe- daliera Policlinico Sant’Orsola-Malpighi, Semeiotica Medica Bernardi), Vittorio, Durante, Daniela, Tirotta, Giovanna Eusebi (Ospedale di Cattolica, Rimini, Marco, Cattaneo, Maria Valentina Amoruso, Paola, Fracasso, Cristina Fasolino (Azienda ospedaliera San Paolo, Moreno, Tresoldi, Enrica 13 Internal and Emergency Medicine Internal and Emergency Medicine Bozzolo, Sarah Damanti (IRCCS Ospedale San Raffaele, – Milano, Medicina Generale, e delle Cure Avanzate), Massimo, Porta, Miriam Gino (AOU Città della Salute e della Scienza di Torino, – Torino, and Medicina Interna, 1U).

Subjects
Hospital cure, Chronic obstructive pulmonary disease, Heart failure, Mortality, Multimorbidity, Prognosis
Published
2023

39. Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

Author

Germano Orrù, Luchino Chessa, Selene Cipri, Gianmario Usai, Andrea Perra, Michela Miglianti, F. Coghe, Federico Meloni, Mauro Giovanni Carta, Davide Firinu, Giulia Costanzo, M. Conti, Giuseppe Fenu, Marcello Campagna, Stefano Del Giacco, Francesca Sedda, Riccardo Cappai, Roberto Littera, and Marta Secci

Subjects
medicine.medical_specialty, COVID-19 Vaccines, Booster dose, Disease, General Biochemistry, Genetics and Molecular Biology, Immune system, Internal medicine, Autoimmune disease, medicine, Humans, RNA, Messenger, BNT162 Vaccine, Hematology, SARS-CoV-2, business.industry, Immunogenicity, Vaccination, COVID-19, Infant, General Medicine, medicine.disease, Immunoglobulin G, Antibody Formation, Original Article, BNT162b2, Immune-mediated inflammatory diseases, IMID, business
Abstract

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p p = 0.031), T2 (p

Published
2021

40. Eosinophilic Granulomatosis with Polyangiitis Relapse after COVID-19 Vaccination: A Case Report

Author

Giulia Costanzo, Andrea Giovanni Ledda, Alessandra Ghisu, Matteo Vacca, Davide Firinu, and Stefano Del Giacco

Subjects
Pharmacology, relapse, mRNA BNT162b2 vaccine, Infectious Diseases, vaccine, Drug Discovery, Immunology, COVID-19, Medicine, Case Report, Pharmacology (medical), EGPA
Abstract

Background: We here describe the case of a 71-year-old Caucasian woman previously diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA) that had been treated with Mepolizumab, an anti-IL5 monoclonal antibody, since 2019 with a good clinical response. Methods: She had a mild COVID-19 in December 2020 and she tested negative for SARS-CoV-2 infection in only late January 2021. In April 2021 she received the first dose of mRNA BNT162b2 vaccine. Ten days later she developed myalgia, dyspnea and numbness of the limbs due to a relapse of EGPA that occurred during Mepolizumab treatment.

Published
2022

41. Verifying the Theory of Climate Affecting Lethality of COVID-19 by an Analysis in Two Climatic Zones of Chile

Author

Cesar Ivan Aviles-Gonzalez, Alessandra Scano, Giulia Cossu, Roberto Littera, Marcello Campagna, Simona Deidda, Ferdinando Romano, Goce Kalcev, Davide Firinu, Federico Meloni, Mauro Giovanni Carta, Stefano Del Giacco, Angelo Restivo, Luigi Zorcolo, Luigi Marongiu, Giorgio Tamburini, Alberto Maleci, Germano Orrù, Luchino Chessa, and María Verónica Brasesco

Subjects
Community and Home Care, Health (social science), Public Health, Environmental and Occupational Health
Abstract

Introduction: The study of seasonal influences on the COVID-19 pandemic can take advantage of the unique position of Chile and its different climatic profiles in the north-south extension. The purpose is to verify the influence of seasonal climate changes on the COVID-19 in the temperate and sub-arctic areas of Chile. Methods: We monitored the evolution of CFR in temperate versus sub-boreal regions, reporting from the John Hopkins University COVID-19 Center on the CFR in each province in midwinter, spring, and early summer. Results: CFR worsened from mid-winter to mid-spring in the temperate zone of Chile, while in the sub-boreal area the CFR improves in the same period, (Kruskal Wallis Test, p=0.004). In the temperate zone after the increase in late winter-early spring, CRF tends to stabilize; on the contrary in the sub-boreal zone, there is a more marked tendency to worsen the CFR at the same time (Kruskal Wallis Test, p=0.010). The temperate zone of Chile shows a CFR increasing until spring-like temperate Europe, unlike Europe CFR does not decrease in summer, but the mean minimum temperature in temperate Chile is lower in summer than in temperate Europe. In Patagonian, CFR remains stable or drops from winter to spring but increases in early summer. Conclusion: The temperate and sub-boreal zones of Chile have a markedly different CFR variation profile during the COVID-19 pandemic.

Published
2022

42. Differences in lethality and diffusion of Covid-19 in countries using different kinds of vaccines

Author

Mauro Giovanni Carta, Germano Orrù, Ambra Peracchia, Giulia Cossu, Fernanda Velluzzi, Laura Atzori, Caterina Ferreli, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera, Roberto Puxeddu, Luchino Chessa, Davide Firinu, Stefano Del Giacco, Angelo Restivo, Simona Deidda, Alessandra Scano, Ferdinando Coghe, Luigi Minerba, Maria Manconi, and Luca Saba

Abstract

To verify if lethality and diffusivity of Covid-19 correlated with percentage of people vaccinated in different countries and whether results on these indicators were comparable under different types of vaccines. A linear regression analysis was conducted between vaccines/inhabitant, new cases/inhabitants and ratio deaths/cases. A comparison between the three indicators was carried out in countries subdivided by kind of vaccine. The proportion of vaccinations/inhabitants correlates negatively with proportion of deaths × 100 cases ( R = −3.90, p

Published
2022

43. Cofactors in food allergy: a retrospective study on a cohort of Sardinian patients sensitized to Omega-5 gliadin and Pru p 3

Author

Giulia Costanzo, Annalisa Matolo, Laura Saderi, Maria Rita Messina, Davide Firinu, Maria Pina Barca, Paolo Serra, Nicoletta Corso, Giovanni Sotgiu, and Stefano Del Giacco

Abstract

Purpose: Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin.Materials and methods: We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). Results: we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between LTPs+ patients and Tri a 19+ patients that showed, in this latter group, a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure.Conclusions:Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies.

Published
2022

44. Chronic Spontaneous Urticaria: A Low Grade Disseminated Intravascular Coagulation Only Partially Reversed by Omalizumab

Author

Marina Di Pino, Maria Filomena Ruberto, Giulia Anna Maria Luigia Costanzo, Davide Firinu, Maria Sebastiana Piras, Mario Nicola Mura, Stefano Del Giacco, Ferdinando Coghe, Francesco Marongiu, and Doris Barcellona

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology, circulatory and respiratory physiology
Abstract

Chronic spontaneous urticaria (CSU) is a disorder characterized by wheals and/or angioedema. The coagulation cascade and inflammation pathways are closely linked together. The aim of our study was first to investigate the dynamics of clot formation in plasma (Clot Waveform Analysis, CWA) in a group of 47 patients with CSU along with other coagulative parameters dedicated to the study of hypercoagulability such as: D-Dimer, F 1+2 peptide, Fibrinogen, Platelet count and Mean Platelet Volume (MPV). Secondly, 23 out of 47 patients were treated with Omalizumab at four administration intervals from T0 to T4. A statistically significant increase in Activated Partial Thromboplastin (aPTT) ratio, D-Dimer, F1+2, Platelet count and MPV was found when compared with 53 healthy controls (HC). In contrast, the 2nd Derivative of aPTT showed lower values than those of the HC. No differences were found between 1st derivative of aPTT and Fibrinogen. D-Dimer only showed a significant difference between T0 and T3. An activation of both coagulation and fibrinolysis along with a weaker clot acceleration may be in agreement with a low-grade DIC. The accelerated turnover pf platelets expressed by both an increase of platelet count and MPV further support this pathway in CSU. Omalizumab does not affect the relationship between the immune and the haemostatic systems.

Published
2022

45. Impact of Diabetes Mellitus and Its Comorbidities on Elderly Patients Hospitalized in Internal Medicine Wards: Data from the RePoSi Registry

Author

Christiano, Argano, Giuseppe, Natoli, Salvatore, Mularo, Alessandro, Nobili, Marika Lo Monaco, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Argano C., Natoli G., Mularo S., Nobili A., Lo Monaco M., Mannucci P.M., Perticone F., Pietrangelo A., and Corrao S.

Subjects
Leadership and Management, 1-year mortality, cancer, comorbidities, diabetes, heart rate, in-hospital mortality, male sex, Heart rate, Socio-culturale, Health Informatics, comorbidities, Article, Comorbidities, Health Information Management, diabetes, heart rate, cancer, male sex, in-hospital mortality, 1-year mortality, Cancer, Diabetes, In-hospital mortality, Male sex, LS4_4, Health Policy, Medicine, 1-year mortality, Cancer, Comorbidities, Diabetes, Heart rate, In-hospital mortality, Male
Abstract

Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.

Published
2022

46. Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults

Author

Alessio, Novella, Chiara, Elli, Mauro, Tettamanti, Alessandro, Nobili, Aladar, Ianes, Pier Mannuccio Mannucci, Luca, Pasina, Carlotta, Franchi, Gualberto, Gussoni, Stefano, Bonassi, Antonella, Valerio, Federica, Mammarella, Codjo Djignefa Djade, Raffaella, Rossio, Barbara, Ferrari, Daniela, Mari, Marco, Ferretti, Francesco, Salerno, Alessio, Conca, Antonino, Tuttolomondo, Anna, Cirrincione, Antonio, Pinto, Antonio, Cherubini, Giuseppina, Dell’Aquila, Roberto, Bernabei, Graziano, Onder, Michele, Ciaburri, Dario, Manfellotto, Irene, Caridi, Enzo, Lancia, Alessandra, Forgione, Concetta, Donato, Serra Maria Grazia, Luigi, Lusiani, Bullo, Cristina, Brocco, Stefano, Pedretti, Giovanni, Pattacini, Corrado, Francesco, Violi, Ludovica, Perri, Luigi Di Cioccio, Carlo Di Meo, Laura, Minchella, Moira, Ceci, Alberto, Ferrari, Salvatore, Foderaro, Antonio, Brucato, Anna, Valenti, Silvia, Ghidoni, Renzo, Rozzini, Lina, Falanga, Alessandra, Marengoni, Simona, Ghibelli, Chiara, Mussi, Maria Alice Ferri, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Antonietta Bleve, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, and Federica, Gandolfo.

Subjects
Aging, Comorbidity indices, Health (social science), Socio-culturale, Multimorbidity, Comorbidity, Chronic disease, Hospitalization, Italy, Older adults, Chronic disease, Comorbidity indices, Excessive polypharmacy, Mortality, Multimorbidity, Older adults, Excessive polypharmacy, Polypharmacy, Humans, LS4_4, Geriatrics and Gerontology, Mortality, Gerontology, Aged
Abstract

Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

Published
2022

47. The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet)

Author

Giuliana Giardino, Cinzia Milito, Vassilios Lougaris, Alessandra Punziano, Maria Carrabba, Francesco Cinetto, Riccardo Scarpa, Rosa Maria Dellepiane, Silvia Ricci, Beatrice Rivalta, Francesca Conti, Antonio Marzollo, Davide Firinu, Emilia Cirillo, Gianluca Lagnese, Caterina Cancrini, Baldassare Martire, Maria Giovanna Danieli, Andrea Pession, Angelo Vacca, Chiara Azzari, Giovanna Fabio, Annarosa Soresina, Carlo Agostini, Giuseppe Spadaro, Raffaele Badolato, Maria Pia Cicalese, Alessandro Aiuti, Alessandro Plebani, Isabella Quinti, Claudio Pignata, Giardino, Giuliana, Milito, Cinzia, Lougaris, Vassilio, Punziano, Alessandra, Carrabba, Maria, Cinetto, Francesco, Scarpa, Riccardo, Dellepiane, Rosa Maria, Ricci, Silvia, Rivalta, Beatrice, Conti, Francesca, Marzollo, Antonio, Firinu, Davide, Cirillo, Emilia, Lagnese, Gianluca, Cancrini, Caterina, Martire, Baldassare, Danieli, Maria Giovanna, Pession, Andrea, Vacca, Angelo, Azzari, Chiara, Fabio, Giovanna, Soresina, Annarosa, Agostini, Carlo, Spadaro, Giuseppe, Badolato, Raffaele, Cicalese, Maria Pia, Aiuti, Alessandro, Plebani, Alessandro, Quinti, Isabella, and Pignata, Claudio

Subjects
Adult, Male, SARS-CoV-2, COVID-19, Inborn errors of immunity, Outcome, Seroconversion, Viral shedding, Immunology, Hospitalization, Common Variable Immunodeficiency, Post-Acute COVID-19 Syndrome, Settore MED/02, Immunology and Allergy, Humans, Female, Child, Retrospective Studies
Abstract

COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50–60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p

Published
2022

48. Previous functional social and behavioral rhythms affect resilience to COVID-19-related stress among old adults

Author

Mauro Giovanni Carta, Michele Fornaro, Luigi Minerba, Massimiliano Pau, Fernanda Velluzzi, Laura Atzori, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera, Luchino Chessa, Davide Firinu, Stefano Del Giacco, Angelo Restivo, Simona Deidda, Germano Orrù, Alessandra Scano, Simona Onali, Ferdinando Coghe, Goce Kalcev, and Giulia Cossu

Abstract

Background Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report. Design and methods Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (365 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) atweek-48 (follow-up endpoint)were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS). Results Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score atweek-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI:1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias. Conclusions Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Published
2021

49. Kidney Disease Management in the Hospital Setting: A Focus on Inappropriate Drug Prescriptions in Older Patients

Author

Vincenzo, Arcoraci, Maria Antonietta Barbieri, Michelangelo, Rottura, Alessandro, Nobili, Giuseppe, Natoli, Christiano, Argano, Giovanni, Squadrito, Francesco, Squadrito, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Arcoraci V., Barbieri M.A., Rottura M., Nobili A., Natoli G., Argano C., Squadrito G., Squadrito F., and Corrao S.

Subjects
medicine.medical_specialty, appropriateness of prescription, prescribing patterns, Renal function, Context (language use), RM1-950, Logistic regression, NO, chemistry.chemical_compound, older patient, Internal medicine, hospital setting, medicine, Pharmacology (medical), LS4_4, Medical prescription, prescribing pattern, appropriateness of prescriptions, chronic kidney disease, hospital setting, older patients, prescribing patterns, real-world data, Original Research, Pharmacology, Creatinine, real-world data, business.industry, Retrospective cohort study, medicine.disease, older patients, appropriateness of prescriptions, chronic kidney disease, chemistry, Observational study, Therapeutics. Pharmacology, business, Kidney disease
Abstract

Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.

Published
2021

50. Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy

Author

Davide Firinu, Giuseppe Fenu, Giuseppina Sanna, Giulia A. Costanzo, Andrea Perra, Marcello Campagna, Roberto Littera, Carlotta Locci, Alessandra Marongiu, Riccardo Cappai, Maurizio Melis, Germano Orrù, Stefano Del Giacco, Ferdinando Coghe, Aldo Manzin, and Luchino Chessa

Subjects
COVID-19 Vaccines, Immunoglobulin G, Immunology, COVID-19, Humans, Immunology and Allergy, RNA, Messenger, Antibodies, Viral, Antigens, CD20, BNT162 Vaccine, Immunity, Humoral
Abstract

to investigate the responses to mRNA COVID-19 vaccines in a cohort of immunosuppressed patients affected by immune-mediated inflammatory diseases (IMID).we have measured humoral and cellular immunity using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assays and specific interferon-gamma (IFN-g) release assay (IGRA) before and after the third dose of BNT162b2. The response of those on anti-CD20 (n = 18) was then compared with healthy controls (HC, n = 18) and IMID naïve to anti-CD20 drugs (n = 13).a third BNT162b2 dose is highly immunogenic in IMID patients naïve to anti-CD20, as 100% of the subjects seroconverted compared to the 55% in anti-CD20. The rate of IGRA response was of 79% in anti-CD20, 50% in IMID naïve to anti-CD20, 100% in HC. Among those who have seroconverted, IMID patients had significantly reduced anti-S-IgG and neutralization titers compared to HC, whereas no significant difference was observed when comparing anti-CD20 and HC. Furthermore, 13% of anti-CD20 and 7.7% of IMID were simultaneously negative for both neutralizing antibodies and IGRA after three doses.these data draw attention to the immunogenicity of COVID-19 vaccination in treated IMID, taking specific groups into consideration for vaccination program.

Published
2022

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