Daniele Sola

@uniupo.it

Assistant Professor
Department of Translational Medicine University of Eastern Piedmont

RESEARCH, TEACHING, or OTHER INTERESTS

Internal Medicine, Cell Biology, Immunology and Allergy, Rheumatology

54

Scopus Publications

Scopus Publications

  • Correction to: Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register (Internal and Emergency Medicine, (2023), 18, 4, (1049-1063), 10.1007/s11739-023-03254-3)
    Elena Succurro, Alessio Novella, Alessandro Nobili, Federica Giofrè, Franco Arturi, Angela Sciacqua, Francesco Andreozzi, Antonello Pietrangelo, Giorgio Sesti, Francesco Perticone,et al.

    Springer Science and Business Media LLC

  • Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register
    Elena Succurro, Alessio Novella, Alessandro Nobili, Federica Giofrè, Franco Arturi, Angela Sciacqua, Francesco Andreozzi, Antonello Pietrangelo, Giorgio Sesti, Francesco Perticone,et al.

    Springer Science and Business Media LLC
    AbstractDiabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie–Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria.

  • Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients
    Sebastiano Cicco, Marco D′Abbondanza, Marco Proietti, Vincenzo Zaccone, Chiara Pes, Federica Caradio, Massimo Mattioli, Salvatore Piano, Alberto Maria Marra, Alessandro Nobili,et al.

    Wiley
    AbstractBackgroundHypertension management in older patients represents a challenge, particularly when hospitalized.ObjectiveThe objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients.MethodsA 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.ResultsHypertensive 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.ConclusionsGuidelines‐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.

  • Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
    Ernesto Crisafulli, Giulia Sartori, Alice Vianello, Fabiana Busti, Alessandro Nobili, Pier Mannuccio Mannucci, Domenico Girelli, Pier Mannuccio Mannucci, Giorgio Sesti, Antonello Pietrangelo,et al.

    Springer Science and Business Media LLC
    Abstract Background and objective Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16–2.61) and patients with dementia (HR 1.75, 95% CI 1.06–2.90) had a higher risk of death at one year. The Kaplan–Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population.

  • Transcriptomic profile comparison of monocytes from rheumatoid arthritis patients in treatment with methotrexate, anti-TNFa, abatacept or tocilizumab
    Maria Talmon, Marcella Percio, Joyce Afrakoma Obeng, Federico A. Ruffinatti, Daniele Sola, Pier Paolo Sainaghi, Emanuela Bellis, Stefano Cusinato, Aurora Ianniello, and Luigia G. Fresu

    Public Library of Science (PLoS)
    It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic DMARDs available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFα or abatacept and from healthy donors. Whole-genome transcriptomics yielded a list of regulated genes by Rank Product statistics and DAVID was then used for functional annotation enrichment analysis. Last, data were validated by qRT-PCR. Abatacept, tocilizumab and anti-TNFa cohorts were separately compared with methotrexate, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively. The upper-most ranked genes were related to inflammatory processes and immune responses. Such an approach draws the genomic profile of monocytes in treated RA patients and lays the basis for finding gene signature for tailored therapeutic choices.

  • Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial
    Erica Matino, Elena Tavella, Manuela Rizzi, Gian Carlo Avanzi, Danila Azzolina, Antonio Battaglia, Paolo Becco, Mattia Bellan, Giovanni Bertinieri, Massimo Bertoletti,et al.

    MDPI AG
    As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

  • SARS-CoV-2 infection risk is higher in vaccinated patients with inflammatory autoimmune diseases or liver transplantation treated with mycophenolate due to an impaired antiviral immune response: results of the extended follow up of the RIVALSA prospective cohort
    Manuela Rizzi, Stelvio Tonello, Cristiana Brinno, Erika Zecca, Erica Matino, Micol Cittone, Eleonora Rizzi, Giuseppe Francesco Casciaro, Davide D’Onghia, Donato Colangelo,et al.

    Frontiers Media SA
    BackgroundA relevant proportion of immunocompromised patients did not reach a detectable seroconversion after a full primary vaccination cycle against SARS-CoV-2. The effect of different immunosuppressants and the potential risks for SARS-CoV-2 infection in these subjects is largely unknown.MethodsPatients from the Rivalsa prospective, observational cohort study with planned anti SARS-CoV-2 third dose mRNA vaccination between October and December 2021 were asked to participate to this follow-up study. Patients were asked about eventual confirmed positivity to SARS-CoV-2 infection within 6 months from the third dose and to undergo a blood draw to evaluate seroconversion status after the additional vaccine shot.Results19 out of 114 patients taking part in the survey developed a confirmed SARS-CoV-2 infection; we identified mycophenolate treatment as an independent predictor of an increased risk of infection even after the third vaccine dose (OR: 5.20, 95% CI: 1.70-20.00, p=0.0053). This result is in agreement with the in vitro evidence that MMF impairs both B and T lymphocytes driven immune responses (reduction both in memory B cells producing anti-spike antibodies and in proliferating CD4+ and CD8+ T cells).ConclusionsImmunocompromised patients need an additional vaccine administration to reach a detectable seroconversion, thus fostering a more personalized approach to their clinical management. Moreover, patients undergoing mycophenolate treatment show a specific increased infection risk, with respect to other immunosuppressants thus supporting a closer monitoring of their health status.

  • Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort
    Erika Zecca, Manuela Rizzi, Stelvio Tonello, Erica Matino, Martina Costanzo, Eleonora Rizzi, Giuseppe Francesco Casciaro, Giulia Francesca Manfredi, Antonio Acquaviva, Ileana Gagliardi,et al.

    MDPI AG
    Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of “Maggiore della Carità” University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5–53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8–252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6–54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1–99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9–103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4–204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

  • Increased Levels of ICOS and ICOSL Are Associated to Pulmonary Arterial Hypertension in Patients Affected by Connective Tissue Diseases
    Mattia Bellan, Francesco Murano, Federico Ceruti, Cristina Piccinino, Stelvio Tonello, Rosalba Minisini, Ailia Giubertoni, Daniele Sola, Roberta Pedrazzoli, Veronica Maglione,et al.

    MDPI AG
    Background: Pulmonary hypertension (PH) is a life-threatening complication of connective tissue diseases (CTD); in this study, we aimed at investigating the potential role of inducible co-stimulator (ICOS) and its ligand (ICOS-L) as biomarkers of PH in CTD. Materials and Methods: We recruited 109 patients: 84 CTD patients, 13 patients with CTD complicated by pulmonary arterial hypertension (PAH), and 12 subjects with PAH alone. All recruited patients underwent a complete clinical and instrumental assessment along with quantitative measurement of serum ICOS and ICOS-L. Results: Independently of the underlying cause, patients with PAH were older and had a lower glomerular filtration rate. Interestingly, patients with both CTD-related and CTD-unrelated PAH had higher ICOS and ICOS-L serum concentrations than CTD patients (0.0001 for both). When compared to CTD patients, those affected by CTD-PAH showed higher ICOS (440 (240–600) vs. 170 (105–275) pg/mL, p = 0.0001) and ICOS-L serum concentrations (6000 (4300–7000) vs. 2450 (1500–4100) pg/mL; p = 0.0001). In a logistic regression, ICOS and ICOS-L were associated with a diagnosis of PAH, independently from age, gender, and renal function. The corresponding receiver operating characteristic (ROC) curves demonstrated a good diagnostic performance for both ICOS and ICOS-L. Conclusions: ICOS and ICOS-L are increased in patients with PAH, irrespectively from the underlying cause, and represent promising candidate biomarkers for the diagnostic screening for PAH among CTDs patients.

  • Clinical Relevance of Liver Involvement in the Clinical Course of Systemic Sclerosis
    Maria Lorena, Mattia Bellan, Maia Lepore, Daniele Sola, Roberta Pedrazzoli, Cristina Rigamonti, Carla De Benedittis, Giulia Francesca Manfredi, Antonio Acquaviva, Stelvio Tonello,et al.

    MDPI AG
    Liver involvement in systemic sclerosis (SSc) is rare. We evaluated the prevalence of liver fibrosis and hepatic autoimmunity in SSc patients in a retrospective observational cohort (97 SSc or mixed connective tissue disease with sclerodermic manifestations patients undergoing transient elastography, evaluating liver stiffness (LS) and controlled attenuation parameter (CAP), due to clinical indications along with biochemistry assessments and major antibodies associated to liver autoimmunity). Among them, 11 had LS ≥ 7.5 kPa and 5 showed an LS compatible with cirrhosis (LS ≥ 12.5 kPa). Predictors of LS ≥ 7.5 fibrosis were alcohol consumption (>14 or >7 alcoholic units/week for men and women, respectively), waist circumference (>102 or >88 cm for men and women, respectively), elevated alkaline phosphatase, and anti-La and anti-mitochondrial antibody (AMA) positivity. Six patients had CAP values compatible with severe steatosis (≥280 dB/m). Waist circumference, body mass index and diabetes mellitus were significant predictors of steatosis. Out of 97 patients, 19 were positive for AMA, 4 for anti-Sp100, 1 for anti-Gp210 and 7 were diagnosed with primary biliary cholangitis. Among SSc patients, hepatic fibrosis biomarkers and AMA prevalence are relatively high, suggesting the opportunity of performing a transient elastography and a screening for hepatic autoimmunity at diagnosis and/or during disease progression.

  • A Pilot Study on Clinical Scores, Immune Cell Modulation, and Microbiota Composition in Allergic Patients with Rhinitis and Asthma Treated with a Probiotic Preparation
    Enza Torre, Daniele Sola, Alice Caramaschi, Flavio Mignone, Elisa Bona, and Silvia Fallarini

    S. Karger AG
    <b><i>Background:</i></b> Specific drugs and/or immunotherapies are widely used to treat allergies, but drug-induced adverse effects recently led to explore new additional strategies. We studied whether a probiotic preparation (iPROB®; Anallergo SpA, Florence, Italy) is effective in allergic patients and the mechanisms underlying clinical outcomes. <b><i>Methods:</i></b> Eligible patients (<i>n</i> = 28), all suffering from allergic rhinitis with/without bronchial asthma, were consecutively recruited at the Allergology Medical Unit (Novara, Italy) and treated with this probiotic. From each patient, we collected blood and stool samples at the baseline, after 60 days of probiotic supplementation, and after 60 days from probiotic discontinuation. In each blood sample, the percentage of hematopoietic stem cells, eosinophils, and basophils was measured by FACS. To analyze stool microbiota composition, genomic DNA was extracted, bacterial 16S DNA libraries sequenced by Illumina platform (Miseq), and raw sequences processed. Generated data were statistically analyzed. <b><i>Results:</i></b> Probiotic-treated patients showed a significant decrease in Average Rhinitis Total Symptom Score (<i>d</i> = −10.5714), and Visual Analog Scale (<i>d</i> = −2.00) clinical indices, as well as important improvements in quality of life. In whole blood, a significant reduction in the percentage of activated eosinophils and basophils was determined, and this effect persisted after specific cell stimulation. Consistently, the serum levels of IL-4 and IL-5 decreased after probiotic treatment, suggesting a reduction in the Th2 cytokine profile. In addition, microbiome genomic analysis (<i>n</i> = 6) showed an increase in microbiome biodiversity, which positively correlates with clinical and cellular data. <b><i>Conclusion:</i></b> Present study suggests that iPROB® preparation has clinical/biological properties to be a valid add-on supplementation in allergic patients with asthma and rhinitis.

  • Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry
    Salvatore Corrao, Alessandro Nobili, Giuseppe Natoli, Pier Mannuccio Mannucci, Francesco Perticone, Antonello Pietrangelo, Christiano Argano, Pier Mannuccio Mannucci, Alessandro Nobili, Antonello Pietrangelo,et al.

    Springer Science and Business Media LLC
    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 < 250 mg/dL, respectively (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.

  • Role of osteopontin as a potential biomarker of pulmonary arterial hypertension in patients with systemic sclerosis and other connective tissue diseases (CTDS)
    Mattia Bellan, Cristina Piccinino, Stelvio Tonello, Rosalba Minisini, Ailia Giubertoni, Daniele Sola, Roberta Pedrazzoli, Ileana Gagliardi, Erika Zecca, Elisa Calzaducca,et al.

    MDPI AG
    Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTD). Its early diagnosis is essential to start effective treatment. In the present paper, we aimed to evaluate the role of plasma osteopontin (OPN) as a candidate biomarker of PAH in a cohort of CTD patients. OPN is a pleiotropic protein involved in inflammation and fibrogenesis and, therefore, potentially promising in this specific clinical context. We performed a cross-sectional observational study on a cohort of 113 CTD patients (females N = 101, 89.4%) affected by systemic sclerosis N = 88 (77.9%), mixed connective tissue disease N = 10 (8.8%), overlap syndrome N = 10 (8.8%) or undifferentiated connective tissue disease N = 5 (4.4%). CTD-PAH patients showed significantly higher OPN plasma values than patients with CTD alone (241.0 (188.8–387.2) vs. 200.7 (133.5–281.6) ng/mL; p = 0.03). Although OPN levels were directly correlated with age and inversely with glomerular filtration rate, they remained associated with PAH at multivariate analysis. In conclusion, OPN was significantly associated with PAH among patients with CTD, suggesting it may have a role as a non-invasive disease biomarker of PAH.

  • The multifaceted spectrum of liver cirrhosis in older hospitalised patients: Analysis of the REPOSI registry
    Antonio De Vincentis, Umberto Vespasiani-Gentilucci, Luisa Costanzo, Alessio Novella, Laura Cortesi, Alessandro Nobili, Pier Mannuccio Mannucci, Raffaele Antonelli Incalzi, Pier Mannuccio Mannucci, Alessandro Nobili,et al.

    Oxford University Press (OUP)
    Abstract Background Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. Objectives To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. Methods A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. Results LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age–sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10–1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37–3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. Conclusions LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.

  • Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry
    Christiano Argano, , Nicola Scichilone, Giuseppe Natoli, Alessandro Nobili, Gino Roberto Corazza, Pier Mannuccio Mannucci, Francesco Perticone, and Salvatore Corrao

    Springer Science and Business Media LLC
    Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patients, 932 (19.8%) had a diagnosis of COPD. Patients with COPD had more hospitalization, a significant overt cognitive impairment, a clinically significant disability and more depression in comparison with non-COPD subjects. COPD patients took more drugs, both at admission, in-hospital stay, discharge and 3-month and 1-year follow-up. 14 comorbidities were more frequent in COPD patients. Cerebrovascular disease was an independent predictor of in-hospital mortality. At 3-month follow-up, male sex and hepatic cirrhosis were independently associated with mortality. ICS-LABA therapy was predictor of mortality at in-hospital, 3-month and 1-year follow-up. This analysis showed the severity of impact of COPD and its comorbidities in the real life of internal medicine and geriatric wards.

  • Underdiagnosis and undertreatment of osteoporotic patients admitted in internal medicine wards in Italy between 2010 and 2016 (the REPOSI Register)
    Jessica Pepe, , Pasquale Agosti, Cristiana Cipriani, Mauro Tettamanti, Alessandro Nobili, Luciano Colangelo, Rachele Santori, Mirella Cilli, and Salvatore Minisola

    Springer Science and Business Media LLC
    To evaluate clinical features, treatments, and outcomes of osteoporotic patients admitted to internal medicine and geriatric wards compared with non-osteoporotic patients (REPOSI registry). We studied 4714 patients hospitalized between 2010 and 2016. We reported age, sex, educational level, living status, comorbidities and drugs taken, Cumulative Illness Rating Scale (CIRS), Barthel Index, Short-Blessed Test, 4-item Geriatric Depression Scale, serum hemoglobin, creatinine, and clinical outcomes. Osteoporosis was defined based on the diagnoses recorded at admission, according to the following ICD9: 733, 805–813, 820–823. Twelve percent of the patients had a preadmission diagnosis of osteoporosis. Only 20% of these had been prescribed oral bisphosphonates; 34% were taking vitamin D supplements. Osteoporotic patients were significantly older, with lower BMI, higher CIRS, and taking more drugs. They were significantly more depressed, less independent, with a higher severity of cognitive impairment compared with non-osteoporotic patients. At discharge, the number of patients receiving treatment for osteoporosis did not change. Length of stay and inhospital mortality did not differ between groups. Osteoporotic patients were more frequently nonhome discharged compared with those without osteoporosis (14.8 vs. 7.9%, p = 0.0007), mostly discharged to physical therapy or rehabilitation (8.8 vs. 2.5% of patients, p < 0.0001). Among osteoporotic patients deceased 3 months after discharge, the number of those treated with vitamin D, with or without calcium supplements, was significantly lower compared with survivors (12 vs. 32%, p = 0.0168). The diagnosis of osteoporosis is poorly considered both during hospital stay and at discharge; osteoporotic patients are frailer compared to non-osteoporotic patients.

  • What changed in the Italian internal medicine and geriatric wards during the lockdown
    Barbara D'Avanzo, Alessandro Nobili, Mauro Tettamanti, Luca Pasina, and Pier Mannuccio Mannucci

    Elsevier BV

  • Red cell distribution width is a potential predictor of early relapse in polymyalgia rheumatica
    D. Soddu, D. Sola, M. Bellan, E. Boin, M.G. Cittone, E. Zecca, E. Matino, R. Pedrazzoli, E. Rizzi, A.R. Pedrinelli,et al.

    PAGEPress Publications
    Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p&lt;0.03). In a stepwise logistic regression, RDW (p=0.01) predicted the risk of relapse at 6 months, while age, gender, CRP, ESR, Hb, MCV and prednisone dose did not fit the model. Our results show that RDW is an independent biomarker of early relapse, making this parameter a potentially promising predictive marker in PMR.

  • Simple parameters from complete blood count predict in-hospital mortality in covid-19
    Mattia Bellan, Danila Azzolina, Eyal Hayden, Gianluca Gaidano, Mario Pirisi, Antonio Acquaviva, Gianluca Aimaretti, Paolo Aluffi Valletti, Roberto Angilletta, Roberto Arioli,et al.

    Hindawi Limited
    Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p &lt; 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p &lt; 0.001 ) and gender ( χ 2 17.3; p &lt; 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL   ratio &gt; 4.68 was characterized by an odds ratio for in-hospital mortality   OR = 3.40 (2.40-4.82), while the OR for a RDW &gt; 13.7 % was 4.09 (2.87-5.83); a platelet   count &gt; 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

  • Cardiopulmonary exercise testing is an accurate tool for the diagnosis of pulmonary arterial hypertension in scleroderma related diseases
    Mattia Bellan, Ailia Giubertoni, Cristina Piccinino, Mariachiara Buffa, Debora Cromi, Daniele Sola, Roberta Pedrazzoli, Ileana Gagliardi, Elisa Calzaducca, Erika Zecca,et al.

    MDPI AG
    The early diagnosis of pulmonary arterial hypertension (PAH) is a major determinant of prognosis in patients affected by connective tissue diseases (CTDs) complicated by PAH. In the present paper we investigated the diagnostic accuracy of cardiopulmonary exercise testing (CPET) in this specific setting. We recorded clinical and laboratory data of 131 patients who underwent a CPET at a pulmonary hypertension clinic. Out of them, 112 (85.5%) had a diagnosis of CTDs; 8 (6.1%) received a diagnosis of CTDs-PAH and 11 (8.4%) were affected PH of different etiology. Among CPET parameters the following parameters showed the best diagnostic performance for PAH: peak volume of oxygen uptake (VO2; AUC: 0.845, CI95% 0.767–0.904), ratio between ventilation and volume of exhaled carbon dioxide (VE/VCO2 slope; AUC: 0.888, CI95%: 0.817–0.938) and end-tidal partial pressures (PetCO2; AUC: 0.792, CI95%: 0.709–0.861). These parameters were comparable among CTDs-PAH and PH of different etiology. The diagnostic performance was even improved by creating a composite score which included all the three parameters identified. In conclusion, CPET is a very promising tool for the stratification of risk of PAH among CTDs patients; the use of composite measures may improve diagnostic performance.

  • Pain and Frailty in Hospitalized Older Adults
    Ilaria Ardoino, Carlotta Franchi, Alessandro Nobili, Pier Mannuccio Mannucci, Oscar Corli, Pier Mannuccio Mannucci, Alessandro Nobili, Antonello Pietrangelo, Francesco Perticone, Giuseppe Licata,et al.

    Springer Science and Business Media LLC
    Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people.

  • Overlapping polyclonal lymphoproliferative disorders
    Francesco Gavelli, Ramona Bonometti, Mattia Bellan, Daniele Sola, Antonello Gibbin, Filippo Patrucco, Paolo Spina, Alessandro Gualerzi, Serena Favretto, LuigiMario Castello,et al.

    Scientific Scholar
    Multicentric Castleman disease (MCD) is a rare clinical entity characterized by a polyclonal lymphoid proliferation, leading to generalized lymphadenopathy, organomegaly and systemic symptoms. It has been reported in association with either other monoclonal or polyclonal lymphoid disorders, such as POEMS syndrome and immunoglobulin (Ig)G4-related disease. We present a patient showing a variant of MCD, sharing common features with POEMS syndrome and associated with the proliferation of IgG4-producing plasma cells.

  • Role of positron emission tomography in the assessment of disease burden and risk of relapse in patients affected by giant cell arteritis
    Mattia Bellan, Erinda Puta, Alessandro Croce, Gian Mauro Sacchetti, Federica Orsini, Erika Zecca, Daniele Soddu, Francesco Gavelli, Gian Carlo Avanzi, Luigi Castello,et al.

    Springer Science and Business Media LLC

  • Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
    Mattia Bellan, Arnaldo Dimagli, Cristina Piccinino, Ailia Giubertoni, Aurora Ianniello, Federico Grimoldi, Maurizio Sguazzotti, Alessandra Nerviani, Michela Barini, Alessandro Carriero,et al.

    Hindawi Limited
    Background. Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). Aims. To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. Methods. In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. Results. Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K–W variance p&lt;0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K–W, p≤0.05). Plasma sMer≥19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p&lt;0.03). Values of Gas6≤24.5 ng/ml and of sAxl≤15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p&lt;0.001; sAxl AUC 0.705, p&lt;0.05). Conclusions. The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

  • Association between red cell distribution width and response to methotrexate in rheumatoid arthritis
    M. Bellan, D. Soddu, E. Zecca, A. Croce, R. Bonometti, R. Pedrazzoli, D. Sola, C. Rigamonti, L.M. Castello, G.C. Avanzi,et al.

    PAGEPress Publications
    Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p&lt;0.0001). The increase of RDW was greater among patients with good EULAR response, becoming progressively smaller in cases with moderate and poor response (1.0% [0.4-1.4] vs. 0.7 [0.1-2.0] vs. 0.3 [-0.1-0.8]; p=0.03). RDW is a strong predictor of early response to MTX in RA. RDW significantly increases after MTX initiation in parallel to treatment response, suggesting a role as a marker of MTX effectiveness.