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1. IR (index of reactivity)-house dust mite sublingual immunotherapy liquid formulation for allergic rhinoconjunctivitis: Systematic review and meta-analysis of randomized and nonrandomized studies

Author: Danilo Di Bona, MD, PhD, Palma Carlucci, MD, Federico Spataro, MD, Giovanni Paoletti, MD, Josiane Cognet-Sicé, PharmD, Silvia Scurati, PhD, and Giorgio Walter Canonica, MD
Subjects: Guidelines, nonrandomized studies, randomized controlled trials, real-life, rhinoconjunctivitis, study quality, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Although randomized controlled trials (RCT) are the reference standard of evidence in allergen immunotherapy (AIT), nonrandomized studies (NRS) are needed to confirm their results in more representative populations, particularly for treatment duration and persistence. However, when discrepancies are observed between RCT and NRS, NRS reliability decreases because these discrepant results are generally attributed to the methodologic flaws of NRS. Objective: We compared the benefit of sublingual AIT (SLIT) for allergic rhinoconjunctivitis in NRS versus RCT focusing on a single product/allergen to reduce heterogeneity. Methods: For meta-analysis, house dust mite (HDM) SLIT liquid formulation studies were sourced from computerized (Medline, Web of Science, and LILACS databases, to January 2023) and manual literature searches. Populations, treatments, and outcome data were combined (DerSimonian-Laird method). Noncomparative NRS were compared to RCT’ SLIT arm before and after treatment. Efficacy was determined as the standardized mean difference (SMD) in symptom score (SS) and medication score (MS). Results: Data from 12 NRS (682 patients) and 8 RCT (176 patients) were analyzed. The benefit with index of reactivity (IR)-HDM SLIT liquid formulation was found significant for, first, SS in both NRS (SMD = −1.27; 95% confidence interval [CI], −1.64, −0.90) and RCT (SMD = −0.56; 95% CI, −0.90, −0.21), and second, MS with SMD equal to −1.35 (95% CI, −1.77, −0.93) and −0.46 (95% CI, −0.67, −0.25), respectively. Metaregression showed that symptom improvement was correlated with treatment duration with consistent results in NRS and RCT with 12-month SS data: −0.87 (interquartile range, −1.02, −0.77) and −0.75 (interquartile range, −0.93, −0.41), respectively. Conclusion: This meta-analysis showed comparable clinical benefit of IR-HDM SLIT liquid formulation increasing over time in both NRS and RCT, suggesting that NRS may reliably integrate RCT results and be considered for guidelines.
Published: 2024
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2. Airways Type-2 Related Disorders: Multiorgan, Systemic or Syndemic Disease?

Author: Francesco Giombi, Gian Marco Pace, Francesca Pirola, Michele Cerasuolo, Fabio Ferreli, Giuseppe Mercante, Giuseppe Spriano, Giorgio Walter Canonica, Enrico Heffler, Sebastian Ferri, Francesca Puggioni, Giovanni Paoletti, and Luca Malvezzi
Subjects: chronic rhinosinusitis, asthma, personalized medicine, atopic dermatitis, type-2 inflammation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Chronic rhinosinusitis (CRS) has recently undergone a significant paradigm shift, moving from a phenotypical classification towards an “endotype-based” definition that places more emphasis on clinical and therapeutic aspects. Similar to other airway diseases, like asthma, most cases of CRS in developed countries exhibit a dysregulated type-2 immune response and related cytokines. Consequently, the traditional distinction between upper and lower airways has been replaced by a “united airway” perspective. Additionally, type-2 related disorders extend beyond respiratory boundaries, encompassing conditions beyond the airways, such as atopic dermatitis. This necessitates a multidisciplinary approach. Moreover, consideration of possible systemic implications is crucial, particularly in relation to sleep-related breathing diseases like Obstructive Sleep Apnoea Syndrome (OSAS) and the alteration of systemic inflammatory mediators such as nitric oxide. The trends in epidemiological, economic, and social burden are progressively increasing worldwide, indicating syndemic characteristics. In light of these insights, this narrative review aims to present the latest evidence on respiratory type-2 related disorders, with a specific focus on CRS while promoting a comprehensive perspective on the “united airways”. It also introduces a novel concept: viewing these conditions as a multiorgan, systemic, and syndemic disease.
Published: 2024
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3. Current treatment strategies for seasonal allergic rhinitis: where are we heading?

Author: Erminia Ridolo, Cristoforo Incorvaia, Francesco Pucciarini, Elena Makri, Giovanni Paoletti, and Giorgio Walter Canonica
Subjects: Seasonal allergic rhinitis, Treatment strategy, Symptomatic drugs, Allergen immunotherapy, Personalized medicine, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Introduction Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available. Areas covered This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history. Expert opinion Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.
Published: 2022
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4. Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps

Author: Giovanni Paoletti, MD, Luca Malvezzi, MD, Anna Maria Riccio, BSc, Desideria Descalzi, BSc, Francesca Pirola, MD, Elena Russo, MD, Laura De Ferrari, BSc, Francesca Racca, MD, Sebastian Ferri, MD, Maria Rita Messina, MD, Francesca Puggioni, MD, Emanuele Nappi, MD, Diego Bagnasco, MD, Frank Rikki Canevari, MD, Fabio Grizzi, BSc, Giuseppe Mercante, MD, Giuseppe Spriano, MD, Giorgio Walter Canonica, MD, and Enrico Heffler, MD
Subjects: Chronic rhinosinusitis with nasal polyps, Nasal cytology, Type-2 inflammation, Biomarkers, Diagnostic tool, Immunologic diseases. Allergy, RC581-607
Abstract: Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Results: Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Conclusions: Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.
Published: 2022
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5. Critical evaluation of asthma biomarkers in clinical practice

Author: Giuseppe Guida, Diego Bagnasco, Vitina Carriero, Francesca Bertolini, Fabio Luigi Massimo Ricciardolo, Stefania Nicola, Luisa Brussino, Emanuele Nappi, Giovanni Paoletti, Giorgio Walter Canonica, and Enrico Heffler
Subjects: asthma, biomarkers, airway inflammation, eosinophils, exhaled nitric oxide (FENO), sputum, Medicine (General), R5-920
Abstract: The advent of personalized medicine has revolutionized the whole approach to the management of asthma, representing the essential basis for future developments. The cornerstones of personalized medicine are the highest precision in diagnosis, individualized prediction of disease evolution, and patient-tailored treatment. To this aim, enormous efforts have been established to discover biomarkers able to predict patients' phenotypes according to clinical, functional, and bio-humoral traits. Biomarkers are objectively measured characteristics used as indicators of biological or pathogenic processes or clinical responses to specific therapeutic interventions. The diagnosis of type-2 asthma, prediction of response to type-2 targeted treatments, and evaluation of the risk of exacerbation and lung function impairment have been associated with biomarkers detectable either in peripheral blood or in airway samples. The surrogate nature of serum biomarkers, set up to be less invasive than sputum analysis or bronchial biopsies, has shown several limits concerning their clinical applicability. Routinely used biomarkers, like peripheral eosinophilia, total IgE, or exhaled nitric oxide, result, even when combined, to be not completely satisfactory in segregating different type-2 asthma phenotypes, particularly in the context of severe asthma where the choice among different biologics is compelling. Moreover, the type-2 low fraction of patients is not only an orphan of biological treatments but is at risk of being misdiagnosed due to the low negative predictive value of type-2 high biomarkers. Sputum inflammatory cell analysis, considered the highest specific biomarker in discriminating eosinophilic inflammation in asthma, and therefore elected as the gold standard in clinical trials and research models, demonstrated many limits in clinical applicability. Many factors may influence the measure of these biomarkers, such as corticosteroid intake, comorbidities, and environmental exposures or habits. Not least, biomarkers variability over time is a confounding factor leading to wrong clinical choices. In this narrative review, we try to explore many aspects concerning the role of routinely used biomarkers in asthma, applying a critical view over the “state of the art” and contemporarily offering an overview of the most recent evidence in this field.
Published: 2022
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6. Long-Term Efficacy of Mepolizumab at 3 Years in Patients with Severe Asthma: Comparison with Clinical Trials and Super Responders

Author: Diego Bagnasco, Stefania Nicola, Elisa Testino, Luisa Brussino, Laura Pini, Marco Caminati, Federica Piccardo, Rikki Frank Canevari, Laura Melissari, Alessandro Ioppi, Luca Guastini, Carlo Lombardi, Manlio Milanese, Francesca Losa, Michela Robbiano, Laura De Ferrari, Anna Maria Riccio, Giuseppe Guida, Marco Bonavia, Donatella Fini, Francesco Balbi, Cristiano Caruso, Pierluigi Paggiaro, Francesco Blasi, Enrico Heffler, Giovanni Paoletti, Giorgio Walter Canonica, Gianenrico Senna, Giovanni Passalacqua, and on behalf of SANI
Subjects: severe asthma, eosinophils, mepolizumab, CRSwNP, IL-5, real life, Biology (General), QH301-705.5
Abstract: The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (−84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting.
Published: 2023
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7. Mast Cells in Upper and Lower Airway Diseases: Sentinels in the Front Line

Author: Giovanni Costanzo, Giulia Anna Maria Luigia Costanzo, Lorenzo Del Moro, Emanuele Nappi, Corrado Pelaia, Francesca Puggioni, Giorgio Walter Canonica, Enrico Heffler, and Giovanni Paoletti
Subjects: mast cells, allergy, rhinitis, asthma, rhinosinusitis, nasal polyps, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Mast cells (MCs) are fascinating cells of the innate immune system involved not only in allergic reaction but also in tissue homeostasis, response to infection, wound healing, protection against kidney injury, the effects of pollution and, in some circumstances, cancer. Indeed, exploring their role in respiratory allergic diseases would give us, perhaps, novel therapy targets. Based on this, there is currently a great demand for therapeutic regimens to enfeeble the damaging impact of MCs in these pathological conditions. Several strategies can accomplish this at different levels in response to MC activation, including targeting individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth, or inducing mast cell apoptosis. The current work focuses on and summarizes the mast cells’ role in pathogenesis and as a personalized treatment target in allergic rhinitis and asthma; even these supposed treatments are still at the preclinical stage.
Published: 2023
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8. Artificial intelligence processing electronic health records to identify commonalities and comorbidities cluster at Immuno Center Humanitas

Author: Pierandrea Morandini, Maria Elena Laino, Giovanni Paoletti, Alessandro Carlucci, Tobia Tommasini, Giovanni Angelotti, Jack Pepys, Giorgio Walter Canonica, Enrico Heffler, Victor Savevski, and Francesca Puggioni
Subjects: allergy, artificial intelligence, asthma, clustering, natural language processing, urticaria, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Comorbidities are common in chronic inflammatory conditions, requiring multidisciplinary treatment approach. Understanding the link between a single disease and its comorbidities is important for appropriate treatment and management. We evaluate the ability of an NLP‐based process for knowledge discovery to detect information about pathologies, patients' phenotype, doctors' prescriptions and commonalities in electronic medical records, by extracting information from free narrative text written by clinicians during medical visits, resulting in the extraction of valuable information and enriching real world evidence data from a multidisciplinary setting. Methods We collected clinical notes from the Allergy Department of Humanitas Research Hospital written in the last 3 years and used it to look for diseases that cluster together as comorbidities associated to the main pathology of our patients, and for the extent of prescription of systemic corticosteroids, thus evaluating the ability of NLP‐based tools for knowledge discovery to extract structured information from free text. Results We found that the 3 most frequent comorbidities to appear in our clusters were asthma, rhinitis, and urticaria, and that 991 (of 2057) patients suffered from at least one of these comorbidities. The clusters which co‐occur particularly often are oral allergy syndrome and urticaria (131 patients), angioedema and urticaria (105 patients), rhinitis and asthma (227 patients). With regards to systemic corticosteroid prescription volume by our clinicians, we found it was lower when compared to the therapy the patients followed before coming to our attention, with the exception of two diseases: Chronic obstructive pulmonary disease and Angioedema. Conclusions This analysis seems to be valid and is confirmed by the data from the literature. This means that NLP tools could have significant role in many other research fields of medicine, as it may help identify other important, and possibly previously neglected clusters of patients with comorbidities and commonalities. Another potential benefit of this approach lies in its potential ability to foster a multidisciplinary approach, using the same drugs to treat pathologies normally treated by physicians in different branches of medicine, thus saving resources and improving the pharmacological management of patients.
Published: 2022
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9. Biologics in severe asthma: the role of real-world evidence from registries

Author: Giovanni Paoletti, Jack Pepys, Marta Casini, Danilo Di Bona, Enrico Heffler, Celine Y.Y. Goh, David B. Price, and Giorgio Walter Canonica
Subjects: Diseases of the respiratory system, RC705-779
Abstract: Asthma is one of the most common noncommunicable diseases; in the majority of patients it is well controlled with inhaled bronchodilators and inhaled corticosteroids, but the management of severe asthma has been a significant challenge historically. The introduction of novel biologic drugs in the past few decades has revolutionised the field, presenting physicians with a variety of biologic drugs with different mechanisms for the treatment of severe asthma. It is of crucial importance to evaluate the effectiveness of these drugs by following their “real-life” effectiveness rather than relying solely on their efficacy, established in carefully designed clinical trials, which therefore do not necessarily match the profile of the real-life patient. Understanding the actual effectiveness of the specific drugs in real-life patients is a crucial part of tailoring the right drugs to the right patients. Registries serve as an important tool in obtaining real-life evidence, since they are in effect observational studies, following the entire patient population.
Published: 2022
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10. The Prevalence of Immediate Hypersensitivity Reactions to the BNT162b2 mRNA Vaccine against SARS-CoV-2: Data from the Vaccination Campaign in a Large Academic Hospital

Author: Giovanni Paoletti, Jack Pepys, Maria Chiara Bragato, Sandro Paoletti, Alessandra Piona, Maria Rita Messina, Francesca Racca, Sebastian Ferri, Emanuele Nappi, Giovanni Costanzo, Lorenzo Del Moro, Francesca Puggioni, Giorgio Walter Canonica, Elena Azzolini, and Enrico Heffler
Subjects: SARS-CoV-2, COVID-19, vaccine, allergy, hypersensitivity, Medicine
Abstract: The anti-SARS-CoV-2 vaccination has probably been the most effective tool for preventing the infection and negative outcomes of the COVID-19 disease, and therefore for interrupting the pandemic state. The first licensed SARS-CoV-2 vaccine was BNT162b2, an mRNA vaccine that has been widely used since the earliest stages of the global vaccination campaign. Since the beginning of the vaccination campaign, some cases of suspected allergic reactions to BNT162b2 have been described. Epidemiological data, however, have provided reassuring results of an extremely low prevalence of these hypersensitivity reactions to anti-SARS-CoV-2 vaccines. In this article, we describe the results of a survey carried out through the use of a questionnaire, administered to all the health personnel of our university hospital after the first two doses of the BNT162b2 vaccine, which investigated the development of adverse reactions after a vaccination. We analyzed the responses of 3112 subjects subjected to the first dose of the vaccine; among these, 1.8% developed symptoms compatible with allergic reactions and 0.9% with clinical manifestations of possible anaphylaxis. Only 10.3% of the subjects who had allergic reactions after the first injection experienced similar reactions after the second dose and none of them experienced anaphylaxis. In conclusion, the anti-SARS-CoV-2 vaccination is rarely associated with severe allergic reactions and the second dose of vaccine is safe for this group of patients.
Published: 2023
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11. Desensitization Protocols for Anti-SARS-CoV-2 Vaccines in Patients with High Risk of Allergic Reactions

Author: Maria Rita Messina, Carlotta Crisciotti, Laura Pellegrini, Emanuele Nappi, Francesca Racca, Giovanni Costanzo, Lorenzo Del Moro, Sebastian Ferri, Francesca Puggioni, Giorgio Walter Canonica, Enrico Heffler, and Giovanni Paoletti
Subjects: SARS-CoV-2, COVID-19, vaccine, allergy, desensitization, Medicine
Abstract: Vaccines for SAR-CoV-2 are the most effective preventive treatment able to reduce the risk of contracting the infection and experiencing worse outcomes whenever the infection is contracted. Despite their rarity, hypersensitivity reactions to the anti-SARS-CoV-2 vaccine have been described and could become the reason not to complete the vaccination. Desensitization protocols for other vaccines have been described and validated, while the use of this approach for anti-SARS-CoV-2 vaccines is still anecdotal. We herein describe our experience with 30 patients with previous allergic reactions to anti-SARS-CoV-2 vaccines or to any of their excipients, proving that they are effective and safe; only two patients experienced hypersensitivity reaction symptoms during the desensitization procedure. Moreover, in this article, we propose desensitization protocols for the most common anti-SARS-CoV-2 vaccines.
Published: 2023
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12. Polyethylene Glycol and Polysorbate 80 Skin Tests in the Context of an Allergic Risk Assessment for Hypersensitivity Reactions to Anti-SARS-CoV-2 mRNA Vaccines

Author: Emanuele Nappi, Francesca Racca, Alessandra Piona, Maria Rita Messina, Sebastian Ferri, Donatella Lamacchia, Giuseppe Cataldo, Giovanni Costanzo, Lorenzo Del Moro, Francesca Puggioni, Giorgio Walter Canonica, Enrico Heffler, and Giovanni Paoletti
Subjects: SARS-CoV-2, vaccine, allergy, polyethylene glycol, polysorbate, skin tests, Medicine
Abstract: Concern has arisen about hypersensitivity reactions in patients with allergic reactions to drugs containing polyethylene glycol (PEG) or polysorbate 80 (PS80), excipients of currently available anti-SARS-CoV-2 mRNA vaccines. However, the actual utility of PEG and PS80 skin allergy testing is currently still debated. We retrospectively analyzed all cases of patients on whom we performed allergometric skin tests for PEG and PS80 in the context of a pre-vaccination screening (for patients with multiple hypersensitivity reactions to drugs for which these excipients were among the suspected agents) or following suspected hypersensitivity reactions to anti-SARS-CoV-2 vaccines. A total of 134 tests were performed for PEG and PS80, eight of which produced uninterpretable results (due to dermographism or non-specific reactions). Of the remaining 126 cases (85 pre-vaccinal and 41 post-vaccine reactions), 16 (12.7%) were positive for PEG and/or PS80. Stratifying by clinical indication, there were no statistically significant differences in the proportion of positive tests between patients evaluated in the context of the pre-vaccination screening and those evaluated after a vaccine reaction (10.6% vs. 17.1%, respectively, p = 0.306). Allergometric skin tests for PEG and PS80 in our case series resulted positive in an unexpectedly high proportion of patients, suggesting that testing for allergy to these two excipients should not be ignored in case of reasonable clinical suspicion.
Published: 2023
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13. Allergy clinics in times of the SARS-CoV-2 pandemic: an integrated model

Author: Giacomo Malipiero, Enrico Heffler, Corrado Pelaia, Francesca Puggioni, Francesca Racca, Sebastian Ferri, Lina Spinello, Morena Merigo, Donatella Lamacchia, Giuseppe Cataldo, Melissa Sansonna, Giorgio Walter Canonica, and Giovanni Paoletti
Subjects: Allergy, Asthma, COVID-19, SARS-CoV-2, Pandemic, Immunotherapy, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Almost the entire World is experiencing the Coronavirus-Disease-2019 (COVID-19) pandemic, responsible, at the end of May 2020, of more than five million people infected worldwide and about 350,000 deaths. In this context, a deep reorganization of allergy clinics, in order to ensure proper diagnosis and care despite of social distancing measures expose, is needed. Main text The reorganization of allergy clinics should include programmed checks for severe and poorly controlled patients, application of digital medicine service for mild-to-moderate disease in well-controlled ones, postponement of non urgent diagnostic work-ups and domiciliation of therapies, whenever possible. As far as therapies, allergen immunotherapy (AIT) should not be stopped and sublingual immunotherapy (SLIT) fits perfectly for this purpose, since a drug home-delivery service can be activated for the entire pandemic duration. Moreover, biologic agents for severe asthma, chronic spontaneous urticaria and atopic dermatitis should be particularly encouraged to achieve best control possible of severe disease in times of COVID-19 and, whenever possible, home-delivery and self-administration should be the preferred choice. Conclusion During COVID-19 pandemic, allergists have the responsibility of balancing individual patients’ needs with public health issues, and innovative tools, such as telemedicine and digital medicine services, can be helpful to reduce the risk of viral spreading while delivering up-to-date personalized care.
Published: 2020
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14. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

Author: Francesca Racca, Gaia Pellegatta, Giuseppe Cataldo, Edoardo Vespa, Elisa Carlani, Corrado Pelaia, Giovanni Paoletti, Maria Rita Messina, Emanuele Nappi, Giorgio Walter Canonica, Alessandro Repici, and Enrico Heffler
Subjects: eosinophilic esophagitis, type 2 inflammation, therapeutic targets, precision medicine, pathophysiology, Physiology, QP1-981
Abstract: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.
Published: 2022
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15. Allergen immunotherapy for respiratory allergy: Quality appraisal of observational comparative effectiveness studies using the REal Life Evidence AssessmeNt Tool. An EAACI methodology committee analysis

Author: Danilo DiBona, Giovanni Paoletti, Derek K. Chu, Jack Pepys, Luigi Macchia, Enrico Heffler, and Giorgio Walter Canonica
Subjects: AIT, RELEVANT, respiratory allergy, SCIT, SLIT, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Observational comparative effectiveness studies in allergen immunotherapy (AIT) represent an important evidence source answering research questions that can be challenging to obtain from randomized controlled trials (RCTs), such as long‐term benefits of AIT, the effects on asthma prevention and the onset of new allergen sensitizations. However, observational studies are prone to several sources of bias, which limit their reliability. The REal Life Evidence AssessmeNt Tool (RELEVANT) was recently developed to assist in quality appraisal of observational comparative research to enable identification of useful nonrandomized studies to be considered within guideline development. Objective To systematically appraise the quality of published observational comparative AIT studies using RELEVANT. Methods Observational studies comparing AIT to pharmacotherapy for respiratory allergies, assessing as outcome measures reduction of symptoms and/or medication use reduction, were retrieved by computerized bibliographic searches. According to RELEVANT, a failure to meet any one of primary items (background, design, measures, analysis, results, discussion/interpretation, and conflict of interest) represents a critical flaw, significantly undermining the validity of the study results. Results The 14 studies identified supported the benefit of AIT in real‐life, which persists after treatment discontinuation. However, none of them met all the 7 primary RELEVANT criteria. The main defects were reported in the design (28.6% of studies), measures and analysis (64.3% of studies), and results (78.6% of studies) items, due to selection bias and lack of methods for adjusting controls. Half of the studies did not report on conflict of interest. Conclusion There is a need for more robust observational research in AIT. RELEVANT appears as an easy‐to‐use and sensitive tool for quality appraisal in AIT studies.
Published: 2021
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16. Immunostimulants in respiratory diseases: focus on Pidotimod

Author: Francesca Puggioni, Magna Alves-Correia, Manar-Farouk Mohamed, Niccolò Stomeo, Riccardo Mager, Massimiliano Marinoni, Francesca Racca, Giovanni Paoletti, Gilda Varricchi, Veronica Giorgis, Giovanni Melioli, Giorgio Walter Canonica, and Enrico Heffler
Subjects: Pidotimod, Immumostimulants, Respiratory diseases, Adaptive immunity, Innate immunity, Allergy, Diseases of the respiratory system, RC705-779
Abstract: Abstract Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections.
Published: 2019
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17. Successful SARS-CoV-2 vaccine allergy risk-management: The experience of a large Italian University Hospital

Author: Giovanni Paoletti, Francesca Racca, Alessandra Piona, Giulio Melone, Morena Merigo, Francesca Puggioni, Sebastian Ferri, Elena Azzolini, Michele Lagioia, Donatella Lamacchia, Giuseppe Cataldo, Maurizio Cecconi, Giorgio Walter Canonica, and Enrico Heffler
Subjects: Allergy, Anaphylaxis, COVID-19, Polyethylen glycole, Vaccine, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been approved recently, and public concern regarding the risk of anaphylactic reactions arose after a few cases during the first days of mass vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions. Objective: We describe the allergy work-up protocol implemented for the vaccination campaign in our Center, aiming to allow the greatest number of people to be vaccinated safely. Methods: The protocol included the self-report of a history of suspected drug or vaccine allergies, and subsequent teleconsultation and allergometric tests for PEG and Polysorbate 80 (PS80). A desensitizing protocol of vaccine administration was applied to patients sensitized only to PS80, and to those with a suspect allergic reaction after the first vaccine dose. Results: 10.2% (414 out of 4042) of the entire vaccine population have been screened: only one patient resulted allergic to PEG and therefore excluded from the vaccination. Another patient was sensitized to PS80 only and safely vaccinated applying the desensitizing protocol. Seven subjects without a previous history of allergic disease experienced suspect hypersensitivity reactions to the first administered dose: one of them resulted allergic to PEG and was excluded from the second dose, while the others safely completed the vaccination with the desensitizing protocol. Conclusion: A careful allergological risk-assessment protocol significantly reduces the number of patients who would have avoided SARS-CoV-2 vaccination for their allergies and to effectively identify and manage those rare patients with sensitization to PEGs and/or PS80.
Published: 2021
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18. New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine

Author: Emanuele Nappi, Maria De Santis, Giovanni Paoletti, Corrado Pelaia, Fabrizia Terenghi, Daniela Pini, Michele Ciccarelli, Carlo Francesco Selmi, Francesca Puggioni, Giorgio Walter Canonica, and Enrico Heffler
Subjects: EGPA, ANCA-associated vasculitis, mRNA vaccine, anti-SARS-CoV-2 vaccine, Medicine
Abstract: Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.
Published: 2022
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19. Nasal Polyposis Quality of Life (NPQ): Development and Validation of the First Specific Quality of Life Questionnaire for Chronic Rhinosinusitis with Nasal Polyps

Author: Ilaria Baiardini, Giovanni Paoletti, Alessia Mariani, Luca Malvezzi, Francesca Pirola, Giuseppe Spriano, Giuseppe Mercante, Francesca Puggioni, Francesca Racca, Giulio Melone, Giacomo Malipiero, Sebastian Ferri, Giorgio Walter Canonica, and Enrico Heffler
Subjects: chronic rhinosinusitis, nasal polyps, patient reported outcomes, quality of life, validation, Medicine
Abstract: To date, no disease-specific tool has been available to assess the impact of chronic rhinosinusitis with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). Therefore, the purpose of this study was to develop and validate a questionnaire specifically designed to this aim: the Nasal Polyposis Quality of Life (NPQ) questionnaire. As indicated in the current guidelines, the development and validation of the NPQ occurred in two separate steps involving different groups of patients. The questionnaire was validated by assessing internal structure, consistency, and validity. Responsiveness and sensitivity to changes were also evaluated. In the development process of NPQ an initial list of 40 items was given to 60 patients with CRSwNP; the 27 most significant items were selected and converted into questions. The validation procedure involved 107 patients (mean age 52.9 ± 12.4). NPQ revealed a five-dimensional structure and high levels of internal consistency (Cronbach’s alpha 0.95). Convergent validity (Spearman’ coefficient r = 0.75; p < 0.01), discriminant validity (sensitivity to VAS score), and reliability in a sample of patients with a stable health status (Interclass Coefficient 0.882) were satisfactory. Responsiveness to clinical changes was accomplished. The minimal important difference was 7. NPQ is the first questionnaire for the assessment of HRQoL in CRSwNP. Our results demonstrate that the new tool is valid, reliable, and sensitive to individual changes.
Published: 2022
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20. Interleukin-5 in the Pathophysiology of Severe Asthma

Author: Corrado Pelaia, Giovanni Paoletti, Francesca Puggioni, Francesca Racca, Girolamo Pelaia, Giorgio Walter Canonica, and Enrico Heffler
Subjects: IL-5, eosinophils, T2-high asthma, mepolizumab, reslizumab, benralizumab, Physiology, QP1-981
Abstract: Interleukin-5 (IL-5) exerts a central pathogenic role in differentiation, recruitment, survival, and degranulation of eosinophils. Indeed, during the last years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the powerful actions of IL-5 finalized to the induction, maintenance, and amplification of eosinophilic inflammation. Therefore, IL-5 is a suitable target for add-on biological therapies based on either IL-5 inhibition (mepolizumab, reslizumab) or blockade of its receptor (benralizumab). These modern treatments can result in being definitely beneficial for patients with severe type 2 (T2)-high eosinophilic asthma, refractory to conventional anti-inflammatory drugs such as inhaled and even systemic corticosteroids.
Published: 2019
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21. Il sacro in Durkheim e le sue definizioni

Author: Giovanni Paoletti
Subjects: Sociology (General), HM401-1281
Abstract: Durkheim’s influential conception of the sacred, as the French sociologist formulated it after a quite long and complex elaboration, contains a fundamental dilemma: one should see the sacred as the apotheosis of the superior moral force of society, or as the need that every society has of material objects in order to think itself?
Published: 2017
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22. Intranasal corticosteroid and antihistamine combinations in the treatment of allergic rhinitis: the role of the novel formulation olopatadine/mometasone furoate

Author: Erminia Ridolo, Alessandro Barone, Francesca Nicoletta, Giovanni Paoletti, Enrico Heffler, Luca Malvezzi, and Giorgio Walter Canonica
Subjects: Immunology, Immunology and Allergy
Published: 2023

23. Local Allergic Rhinitis: Lights and Shadows of a Mysterious Entity

Author: Giulio Melone, Veronica Giorgis, Marina Di Pino, Corrado Pelaia, Emanuele Nappi, Enrico Heffler, Massimo Landi, Matteo Gelardi, and Giovanni Paoletti
Subjects: Nasal Provocation Tests, Immunology, Humans, Immunology and Allergy, Prospective Studies, General Medicine, Immunoglobulin E, Allergens, Rhinitis, Allergic, Rhinitis, Skin Tests
Abstract: Local allergic rhinitis (LAR) is, to date, a debated and complex entity, still orphan of global consideration and a multicentric approach. LAR does not seem to find a proper positioning in the classic classifications and phenotypes of chronic rhinitis, and its pathophysiology relies specifically on the presence of local IgE. These patients in fact have a suggestive clinical history of allergic rhinitis in the presence of negative skin prick tests and serum IgE tests for the suspect allergen. Nasal allergen challenge, assessment of local IgE, basophil activation test (BAT), and nasal cytology are, at the moment, the most used tests in the diagnostic approach to the disease, despite their limitations. Considering that the correct interpretation of diagnostic tests and their clinical relevance is fundamental in the assessment of the right diagnosis and the subsequent therapy, we propose a new diagnostic approach that encompasses all of these methodologies and suggest that several pragmatic randomized control trials as well as prospective, multicentric studies directed at the long-term follow-up of LAR be carried out to further investigate this debated entity.
Published: 2022

24. Biologics and airway remodeling in severe asthma

Author: Gilda Varricchi, Sebastian Ferri, Jack Pepys, Remo Poto, Giuseppe Spadaro, Emanuele Nappi, Giovanni Paoletti, Johann Christian Virchow, Enrico Heffler, Walter G. Canonica, Varricchi, Gilda, Ferri, Sebastian, Pepys, Jack, Poto, Remo, Spadaro, Giuseppe, Nappi, Emanuele, Paoletti, Giovanni, Christian Virchow, Johann, Heffler, Enrico, and G Canonica, Walter
Subjects: Biological Products, Immunology, Keywords: airway remodeling, respiratory system, Asthma, respiratory tract diseases, Airway Obstruction, Pulmonary Disease, Chronic Obstructive, immunotherapie, biomarker, severe asthma, Humans, Airway Remodeling, Immunology and Allergy, biologic, Lung
Abstract: Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a “fixed” bronchial obstruction due to structural changes unresponsive to current therapies, from a “reversible” one as demonstrated by lung function normalization during biological therapies not previously obtained even with high dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent tissue-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert “fixed” remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.
Published: 2022

25. Prevalence of familial link in patients affected by chronic rhinosinusitis with nasal polyposis

Author: Francesco Giombi, Alejandra Carrón‐Herrero, Francesca Pirola, Giovanni Paoletti, Emanuele Nappi, Elena Russo, Armando De Virgilio, Giuseppe Mercante, Giorgio Walter Canonica, Giuseppe Spriano, Enrico Heffler, and Luca Malvezzi
Subjects: Nasal Polyps, Otorhinolaryngology, Chronic Disease, Prevalence, Humans, Immunology and Allergy, Sinusitis, Rhinitis
Published: 2022

26. Oral Corticosteroid Abuse and Self-Prescription in Italy: A Perspective from Community Pharmacists and Sales Reports before and during the COVID-19 Era

Author: Emanuele Nappi, Enrico Keber, Giovanni Paoletti, Marta Casini, Carolina Carosio, Flora Romano, Nicolina Floris, Claudio Parmigiani, Carlo Salvioni, Luca Malvezzi, Francesca Puggioni, Giorgio Walter Canonica, Enrico Heffler, and Corrado Giua
Subjects: Medicine (miscellaneous), oral corticosteroids, abuse, Italy, pharmacists, COVID-19
Abstract: (1) Background: Corticosteroids are commonly used for a variety of conditions, but their use might come with significant side effects. Self-medication practices increased during the COVID-19 pandemic, potentially favoring corticosteroid misuse. Studies on this topic are lacking, thus we aim to characterize the misuse of corticosteroids in Italy through pharmacists’ perspectives and sales reports. (2) Methods: We sent to territorial pharmacists a survey that aimed to investigate corticosteroid misuse before and during the pandemic. In parallel, sales reports of the major oral corticosteroids were obtained from IQVIA. (3) Results: We found that 34.8% of clients demanded systemic corticosteroids without a valid prescription, with a rise to 43.9% during the pandemic (p < 0.001). Adults and patients suffering from upper airway diseases or obstructive airway diseases most frequently asked for corticosteroids without an appropriate prescription. The greatest increase after the beginning of the pandemic was seen for lung diseases. Although sales of the major oral corticosteroids decreased during the pandemic, sales of those used for COVID-19 increased. (4) Conclusions: Self-medication with corticosteroids is common and might lead to avoidable toxicities. This tendency increased during the pandemic probably because of incorrect beliefs about the inappropriate use of corticosteroids for treating COVID-19 itself. The development of shared strategies between doctors and pharmacists is essential in defining protocols guiding appropriate patient referral in order to minimize corticosteroid misuse.
Published: 2023
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27. Comparison of evidence of treatment effects in randomized and nonrandomized studies on allergen immunotherapy

Author: Danilo Di Bona, Palma Carlucci, Federico Spataro, Giovanni Paoletti, Enrico Heffler, Jaakko Pulkanen, Luigi Macchia, Stefano Del Giacco, Ioana Agache, Marek Jutel, Holger J. Schünemann, and Giorgio Walter Canonica
Subjects: Immunology, Immunology and Allergy
Published: 2023

28. Care for Patients with Type-2 Chronic Rhinosinusitis

Author: Gianmarco Giunta, Francesca Pirola, Francesco Giombi, Giovanna Muci, Gian Marco Pace, Enrico Heffler, Giovanni Paoletti, Francesca Puggioni, Michele Cerasuolo, Fabio Ferreli, Fabrizio Salamanca, Giuseppe Mercante, Giuseppe Spriano, Giorgio Walter Canonica, and Luca Malvezzi
Subjects: Medicine (miscellaneous), chronic rhinosinusitis, nasal polyps, personalized medicine, monoclonal antibodies, type-2 inflammation, sinus surgery
Abstract: In the last 20 years, growing interest in chronic rhinosinusitis (CRS) has become evident in medical literature; nevertheless, it is still difficult to identify the real prevalence of the disease. Epidemiological studies are few and focused on heterogeneous populations and diagnostic methods. Recent research has contributed to identifying CRS as a disease characterized by heterogeneous clinical scenarios, high impact on quality of life, and elevated social costs. Patient stratification with phenotypes and identification of the pathobiological mechanism at the origin of the disease (endotype) and its comorbidities are pivotal in the diagnostic process, and they should be addressed in order to properly tailor treatment. A multidisciplinary approach, shared diagnostic and therapeutic data, and follow-up processes are therefore necessary. Oncological multidisciplinary boards offer models to imitate in accordance with the principles of precision medicine: tracing a diagnostic pathway with the purpose of identifying the patient’s immunological profile, monitoring therapeutical processes, abstaining from having only a single specialist involved in treatment, and placing the patient at the center of the therapeutic plan. Awareness and participation from the patient’s perspective are fundamental steps to optimize the clinical course, improve quality of life, and reduce the socioeconomic burden.
Published: 2023
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29. Use, Abuse, and Misuse of Nasal Medications: Real-Life Survey on Community Pharmacist’s Perceptions

Author: Elena Russo, Francesco Giombi, Giovanni Paoletti, Enrico Heffler, Giorgio Walter Canonica, Francesca Pirola, Giuseppe Mercante, Giuseppe Spriano, Luca Malvezzi, Enrico Keber, null SGCP, and Corrado Giua
Subjects: Medicine (miscellaneous), pharmacy, nasal spray, chronic rhinosinusitis, topic steroids, decongestants, allergic rhinitis
Abstract: Background: Medication overuse is an increasing global problem, especially for those rhinology diseases whose management requires over-the-counter drugs. This observational community pharmacy-based study aimed to investigate the actual use of the best-selling topical nasal medications and to characterize the clinical issues underlying their query through the pharmacist’s perception. Methods: In the pilot phase, a preliminary survey was developed by a team of researchers and tested on a small sample of practitioners to assess usability and intelligibility. Eventual amendments were made according to the feedback obtained, and the final version was submitted to practitioners working in 376 pharmacies evenly distributed over the Italian territory. Results: Two groups of customers (18–30 years old and 60–75 years old) were the ones who most frequently purchased topical decongestants. The dosage applied for sympathomimetic amines was higher than recommended in up to 44.4% and the duration of use longer than 5 days in up to 31.9% of the cases. Patients’ queries of alpha agonists and topical corticosteroids resulted in significantly higher numbers than practitioners’ prescriptions. Allergic rhinitis was the most common disease affecting patients seeking sympathomimetic amines. Conclusions: The prolonged use of sympathomimetic amines in patients suffering from rhinology diseases is a significant problem that requires greater attention in terms of social education and surveillance.
Published: 2023
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30. Durkheim, Bergson et la philosophie au collège de France, 1901-1958

Author: Giovanni Paoletti
Subjects: General Social Sciences
Published: 2022

31. 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

32. Exhaled nitric oxide in asthma: from diagnosis to management

Author: Giuseppe Guida, Vitina Carriero, Francesca Bertolini, Stefano Pizzimenti, Enrico Heffler, Giovanni Paoletti, and Fabio L.M. Ricciardolo
Subjects: Breath Tests, Exhalation, Immunology, Immunology and Allergy, Humans, Nitric Oxide, Glucocorticoids, Asthma, Biomarkers
Abstract: Exhaled nitric oxide (FENO) is a noninvasive marker of eosinophilic airway inflammation, therefore, highly informative in asthma. Although FENO measurement is a potentially accessible tool to many physicians, recommendations regarding its clinical utility in diagnosing or tailoring treatment have not reached the expected diffusion. More recently FENO emerged as a biomarker for type-2 asthma phenotyping and a predictor of response to biologics.The physiological discoveries and relevant acquisitions in clinical practice regarding FENO in asthma are presented. The FENO story draw a wavy path, characterized by promising findings, exciting confirmations and periods of low visibility. FENO emerged as a tool to increase the probability of asthma diagnosis. FENO predicts response to inhaled glucocorticoids (ICS), favoring the development of tailored treatment strategies and unrevealing nonadherence to ICS in difficult-to-treat or uncontrolled asthma. Finally, FENO was associated with a more severe phenotype and became a consolidated biomarker of type-2 inflammation.FENO demonstrated to be a noninvasive and very reproducible test, encompassing many applications in the field of asthma management. Its routinely use, according to international guidelines, may improve the quality of patient assistance, from difficult-to-treat cases to biologic monitoring.
Published: 2023

33. 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

34. Diagnostic delay and misdiagnosis in eosinophilic oesophagitis

Author: Gaia Pellegatta, Matteo Ghisa, Alessandro Vanoli, Alessandro Repici, Roberto Penagini, Marco Vincenzo Lenti, Catherine Klersy, Sebastiano Ziola, Antonio Di Sabatino, Aurelio Mauro, Valeria Longoni, Elena Arsiè, Giorgio Laserra, Nicola de Bortoli, F. Racca, Mentore Ribolsi, Giovanni Paoletti, Salvatore Tolone, Fabiana Zingone, A. Sostilio, Edoardo Savarino, Stefania Merli, Elisa Marabotto, Brigida Barberio, and Ludovico Docimo
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Delayed Diagnosis, dysphagia, Food impaction, Young Adult, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Chart review, medicine, Humans, In patient, Diagnostic Errors, Retrospective Studies, oesophagus, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Eosinophilic oesophagitis, Mean age, Eosinophilic Esophagitis, gastro-oesophageal reflux disease, Middle Aged, food impaction, Dysphagia, Endoscopy, 030220 oncology & carcinogenesis, Female, eosinophils, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised.To assess the diagnostic delay in patients with EoE and to explore its risk factors.EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed.261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker,1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay.EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors.
Published: 2021

35. 3. Some Concepts of ‘Evil’ in Durkheim’s Thought

Author: Giovanni Paoletti
Published: 2022

36. Émile Durkheim: Sociology as an Open Science

Author: Giovanni Paoletti and Massimo Pendenza
Published: 2022

37. Durkheim and the History of Religions

Author: Giovanni Paoletti
Published: 2022

38. Outcomes of Non-Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience

Author: Francesca Pirola, Gian Marco Pace, Francesco Giombi, Enrico Heffler, Giovanni Paoletti, Emanuele Nappi, William Sanità, Gaia Giulietti, Gianmarco Giunta, Fabio Ferreli, Giuseppe Mercante, Giuseppe Spriano, Giorgio Walter Canonica, and Luca Malvezzi
Subjects: Otorhinolaryngology
Abstract: The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery.A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries.Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p = 0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p = 0.010, p = 0.002, p = 0.016, respectively); RFS difference resulted significant (log-rank test = 4.16; p = 0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p = 0.001), as well as VAS scores (p = 0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot.The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure.Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 2022.
Published: 2022

39. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author: Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, 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Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, 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, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, 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, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F
Subjects: Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract: Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.
Published: 2021

40. Mechanisms of Allergen Immunotherapy and Potential Biomarkers for Clinical Evaluation

Author: Umit M. Sahiner, Mattia Giovannini, Maria M. Escribese, Giovanni Paoletti, Enrico Heffler, Montserrat Alvaro Lozano, Domingo Barber, Giorgio Walter Canonica, and Oliver Pfaar
Subjects: Medicine (miscellaneous)
Abstract: Allergen-immunotherapy (AIT) is an efficacious and disease-modifying treatment option for IgE-mediated diseases. Among these allergic rhinitis, insect venom allergy, food allergy, and allergic asthma are the most common candidates for AIT. AIT gives rise to clinical immunotolerance which may last for years after the treatment cessation. Mechanisms of AIT include suppression of allergic inflammation in target tissues and stimulation of the production of blocking antibodies, especially IgG4 and IgA. These mechanisms are followed by a reduction of underlying allergen-specific Th2 cell-driven responses to the allergens. Tolerance induction takes place through the desensitization of effector cells and stimulation of regulatory T cells that show their effects by mechanisms involving cell-cell cross-talk, but also other mechanisms, e.g., by the production of immunomodulatory cytokines such as, e.g., IL-10 and TGF-beta. From a personalized medical perspective, there is a need for clinical biomarkers of value in selecting responders and optimizing patient care during AIT. Also, a deeper understanding of underlying mechanistic processes will improve AIT’s future outcomes. In this paper, the current knowledge of mechanisms in AIT is reviewed with a special focus on biomarkers of this therapy.
Published: 2023

41. Evolution in Endoscopic Sinus Surgery: The Adjuvant Role of Reboot Surgery in Patients with Uncontrolled Nasal Symptoms of Eosinophilic Granulomatosis with Polyangiitis

Author: Francesca Pirola, Gianmarco Giunta, Giovanna Muci, Francesco Giombi, Emanuele Nappi, Fabio Grizzi, Enrico Heffler, Giovanni Paoletti, Giorgio Walter Canonica, Giuseppe Mercante, Giuseppe Spriano, Jan Walter Schroeder, and Luca Malvezzi
Subjects: Medicine (miscellaneous)
Abstract: Purpose: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. Methods: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. Results: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. Conclusions: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.
Published: 2023

42. Impact of asthma on bronchiectasis severity and risk of exacerbations

Author: Claudia Crimi, Raffaele Campisi, Nunzio Crimi, Enrico Heffler, Francesca Puggioni, Giovanni Paoletti, Giulia Cacopardo, and Sebastian Ferri
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Exacerbation, viruses, macromolecular substances, Disease, comorbidities, Severity of Illness Index, 03 medical and health sciences, exacerbation, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Asthma, Bronchiectasis, business.industry, Sputum, respiratory system, medicine.disease, Comorbidity, respiratory tract diseases, Eosinophils, 030228 respiratory system, inflammation, Immunoglobulin G, Pediatrics, Perinatology and Child Health, business
Abstract: Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk.We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis of bronchiectasis. All patients were investigated for concomitant diagnosis of asthma. The Bhalla score was used to assess radiological severity of bronchiectasis, and the Bronchiectasis Severity Index (BSI) was used to assess the clinical severity. Blood and sputum samples were collected to assess blood cell count, erythrocyte sedimentation rate, c-reactive protein, immunological status (IgA, IgE, IgM, IgG, and IgG subclasses), and microbiological analysis.A total of 106 patients were enrolled in the study; 30.2% had concomitant asthma and were characterized by higher frequency of bronchiectasis exacerbation, despite higher Bhalla score and lower BSI compared to patients without asthma.The coexistence of asthma and bronchiectasis is associated with an independent increase in the risk of bronchiectasis exacerbation despite lower radiological and clinical severity indexes. Asthmatic airway inflammation could promote an enhanced "Cole's Cycle" that is responsible for a higher frequency of exacerbations.
Published: 2020

43. Gastroesophageal reflux and asthma: when, how, and why

Author: Giulio Melone, Ilaria Baiardini, Giacomo Malipiero, Francesca Puggioni, Francesca Racca, Sebastian Ferri, Giovanni Paoletti, Enrico Heffler, and Giorgio Walter Canonica
Subjects: medicine.medical_specialty, Endotype, Immunology, Comorbidity, Diagnostic tools, Severity of Illness Index, Gastroenterology, Esophageal function, Cost of Illness, Internal medicine, Eosinophilic, Prevalence, medicine, Humans, Immunology and Allergy, In patient, Asthma, business.industry, Reflux, Confounding Factors, Epidemiologic, Proton Pump Inhibitors, medicine.disease, digestive system diseases, Gastroesophageal Reflux, Quality of Life, GERD, business
Abstract: PURPOSE OF REVIEW Gastro-esophageal reflux is a possible cause of uncontrolled symptoms of asthma and should be actively investigated and treated before severe asthma is diagnosed and biological therapy started. RECENT FINDINGS Recent investigations on esophageal function and tissue biomarkers in patients with asthma and associated GERD have established a relevant role for esophageal motility and neuronal sensory abnormalities in linking the two diseases. Characterization of the underpinning inflammatory substrate has showed mixed results as both neutrophilic and eosinophilic type 2 inflammatory changes have been described. SUMMARY New findings regarding inflammatory mechanisms in GERD-associated asthma as well as new diagnostic tools to investigate functional esophageal abnormalities and characterize asthma endotype have identified potential treatable traits that may improve the clinical management and outcome of asthmatic patients with GERD.
Published: 2020

44. Allergen immunotherapy and biologics in respiratory allergy: friends or foes?

Author: Giacomo Malipiero, Ruby Pawankar, Giulio Melone, Giovanni Paoletti, Enrico Heffler, and Francesca Puggioni
Subjects: Allergen immunotherapy, medicine.medical_specialty, Allergy, medicine.medical_treatment, Immunology, Inflammation, Omalizumab, Severity of Illness Index, Immune system, medicine, Humans, Immunology and Allergy, Intensive care medicine, Glucocorticoids, Contraindication, Biological Products, business.industry, Immunotherapy, Allergens, medicine.disease, Combined Modality Therapy, Rhinitis, Allergic, Asthma, Treatment Outcome, Clinical research, Desensitization, Immunologic, medicine.symptom, business, medicine.drug
Abstract: PURPOSE OF REVIEW Allergen-specific immunotherapy has established as an indispensable disease-modifying treatment in allergy practice but its safety and efficacy might be furtherly improved by combining it with other drugs or therapeutic intervention that co-modulate immune type 2 immune networks. RECENT FINDINGS In the past two decades, clinical research focused on AIT and omalizumab co-treatment to improve both safety and long-term efficacy of allergic disease treatment. Recently, combination of AIT with other biologicals targeting different mediators of type 2 inflammation has been set up with interesting preliminary results. Moreover, AIT current contraindication might be overcome by contemporarily controlling underlying type 2 inflammation in severe atopic patients. SUMMARY AIT--biological combination treatment can realize a complex multitargeted treatment strategy allowing for consistently improving disease control and sparing steroid administration.
Published: 2020

45. EDUCATION, SOCIAL LINK AND SOCIAL CHANGE

Author: Giovanni Paoletti
Published: 2022

46. Do the current guidelines for asthma pharmacotherapy encourage over-treatment?

Author: Stefania Nicola, Giuseppe Guida, Giovanni Paoletti, Giovanni Passalacqua, Luisa Brussino, Enrico Heffler, Cristiano Caruso, Elisa Calzolari, Diego Bagnasco, Laura De Ferrari, and Giorgio Walter Canonica
Subjects: Allergen immunotherapy, medicine.medical_specialty, education, MEDLINE, Inhaled corticosteroids, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Medicine, Asthmatic patient, Over treatment, Pharmacology (medical), Intensive care medicine, Asthma, Pharmacology, business.industry, allergen immunotherapy, GINA, ICS/formoterol, inhaled corticosteroids, mild asthma, steroids side effects, General Medicine, medicine.disease, respiratory tract diseases, Airway disease, 030220 oncology & carcinogenesis, business, 030217 neurology & neurosurgery
Abstract: Asthma is a common airway disease, affecting worldwide a percentage of people between 1% and 18%. Although the proper management of asthmatic patients should be ensured by following international d...
Published: 2020

47. Cross-Cultural Validation of the Short Version of the Questionnaire of Olfactory Disorders—Negative Statements into Italian: Towards Personalized Patient Care

Author: Francesca Pirola, Francesco Giombi, Fabio Ferreli, Andrea Costantino, Giuseppe Mercante, Giovanni Paoletti, Enrico Heffler, Giorgio Walter Canonica, Stefano Settimi, Eugenio De Corso, Giuseppe Spriano, and Luca Malvezzi
Subjects: septal deviation, quality of life, chronic rhinosinusitis, questionnaire, Medicine (miscellaneous), Settore MED/31 - OTORINOLARINGOIATRIA, olfactory dysfunction
Abstract: Given the high burden of olfactory dysfunction worldwide, recently increased due to the COVID-19 pandemic, it is mandatory to adopt a specific questionnaire to assess the impact of olfactory impairment on quality of life, to be used in clinical practice. The aim of this study is to adapt and validate the short version of the Questionnaire of Olfactory Disorders-Negative Statements (svQOD-NS) for Italian. In the pilot phase, the Italian version of the questionnaire (ITA-svQOD-NS) was produced following recommended guidelines. It was then given to 50 healthy subjects and 50 patients (affected by either nasal polyposis or septal deviation), and results were compared to those of other widely used questionnaires. Test-retest reliability was assessed on a sample of 25 patients. All 50 patients repeated the questionnaires at one and nine months after surgery. The internal consistency of ITA-svQOD-NS measured with Cronbach α was excellent (α = 0.92). The intraclass correlation coefficient for test-retest reliability was also optimal (0.93; 95%CI: 0.90–0.96). Concurrent validity tested with the Pearson coefficient was significant with all other tests administered; also, concerning responsiveness, statistically significant differences were obtained between pre- and post-operative conditions. ITA-svQOD-NS showed high internal consistency, test-retest reliability, and significant correlation with all most-used clinical questionnaires; thus, it can be efficiently applied to assess olfaction-related QoL in the Italian population.
Published: 2022

48. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

Author: Francesca Racca, Gaia Pellegatta, Giuseppe Cataldo, Edoardo Vespa, Elisa Carlani, Corrado Pelaia, Giovanni Paoletti, Maria Rita Messina, Emanuele Nappi, Giorgio Walter Canonica, Alessandro Repici, and Enrico Heffler
Subjects: eosinophilic esophagitis, Physiology, Physiology (medical), type 2 inflammation, precision medicine, QP1-981, Review, therapeutic targets, pathophysiology
Abstract: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.
Published: 2021

49. Allergen immunotherapy:The growing role of observational and randomized trial 'Real-World Evidence'

Author: Danilo Di Bona, Hans Jürgen Hoffmann, Ralph Mösges, Davide Firinu, Giorgio Walter Canonica, Jon Genuneit, Marek Jutel, Enrico Heffler, Ioana Agache, Giovanni Paoletti, Audrey DunnGalvin, Derek K. Chu, Oliver Pfaar, and Ludger Klimek
Subjects: 0301 basic medicine, Knowledge management, Quality management, Standardization, Computer science, media_common.quotation_subject, Immunology, sublingual immunotherapy, law.invention, Body of knowledge, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, subcutaneous immunotherapy, Hypersensitivity, Humans, Immunology and Allergy, Quality (business), real-world evidence, Randomized Controlled Trials as Topic, media_common, Data collection, business.industry, Reproducibility of Results, Evidence-based medicine, 030104 developmental biology, 030228 respiratory system, Desensitization, Immunologic, randomized controlled trial, allergen immunotherapy, Observational study, business
Abstract: BACKGROUND Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life. METHODS To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real-world" database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. KEY RESULTS There is a need to establish more AIT registries that collect data in a cohesive way, using standardized protocols. CONCLUSIONS This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.
Published: 2021

50. The Use of Molecular Allergy Diagnosis in Anaphylaxis: a Literature Review

Author: Olga Luengo, Francesca Puggioni, Victoria Cardona, Giorgio Walter Canonica, Giovanni Paoletti, Francesca Racca, Giovanni Melioli, and Enrico Heffler
Subjects: Allergy, biology, business.industry, Anaphylactic reaction, Medicine (miscellaneous), medicine.disease, Immunoglobulin E, medicine.disease_cause, Standard procedure, Single test, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Allergen, 030228 respiratory system, Immunology, medicine, biology.protein, Immunology and Allergy, Identification (biology), business, Anaphylaxis
Abstract: Anaphylaxis can be caused mainly by drugs, foods, and hymenoptera or it can be idiopathic, when no cause is identified. The identification of the cause(s) of an anaphylactic reaction can be made by using both top-down (i.e., from patients’ history to MAD) and bottom-up (from MAD screening to the patients’ characterization) strategies. Independently from the strategy, the patients’ history, skin prick test, second, third, and fourth level in vitro serum or cellular assays, and in vivo challenge tests are mandatory. The diagnosis is based on the results of these tests used at best. Third level specific IgE assays, based on the use of molecular allergens, allow a very accurate description of the specific IgE profile of the patient, resulting in a significant support in the identification of the trigger of the anaphylactic reaction. In recent years, this third level has been empowered by the availability of allergen arrays that allow screening a large number of molecular allergens in a single test. In this paper, we analyze the recent scientific literature on this topic, showing that molecular allergy diagnosis does not seem to be yet a standard procedure in the identification of the cause of anaphylaxis.
Published: 2019

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