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1. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology

Author

De Angelis, R, Ferri, C, Giuggioli, D, Bajocchi, G, Dagna, L, Bellando-Randone, S, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Lepri, G, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Cipolletta, E, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Di Vico, C, Gigante, A, Pellagrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Guiducci, S, Doria, A, Salvarani, C, Iannone, F, Matucci-Cerinic, M, Giorgio, A, Alessia, B, Francesca, C, Renato, C, Dall'Ara, F, Angelo, D, Marica, D, Gianluca, S, Rossella, T, De Angelis R., Ferri C., Giuggioli D., Bajocchi G., Dagna L., Bellando-Randone S., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Lepri G., Girelli F., Riccieri V., Zanatta E., Bosello S. L., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A. M., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Cipolletta E., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Di Vico C., Gigante A., Pellagrino G., Pigatto E., Lazzaroni M. -G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Guiducci S., Doria A., Salvarani C., Iannone F., Matucci-Cerinic M., Giorgio A., Alessia B., Francesca C., Renato C., Dall'Ara F., Angelo D. C., Marica D., Gianluca S., Rossella T., De Angelis, R, Ferri, C, Giuggioli, D, Bajocchi, G, Dagna, L, Bellando-Randone, S, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Lepri, G, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Cipolletta, E, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Di Vico, C, Gigante, A, Pellagrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Guiducci, S, Doria, A, Salvarani, C, Iannone, F, Matucci-Cerinic, M, Giorgio, A, Alessia, B, Francesca, C, Renato, C, Dall'Ara, F, Angelo, D, Marica, D, Gianluca, S, Rossella, T, De Angelis R., Ferri C., Giuggioli D., Bajocchi G., Dagna L., Bellando-Randone S., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Lepri G., Girelli F., Riccieri V., Zanatta E., Bosello S. L., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A. M., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Cipolletta E., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Di Vico C., Gigante A., Pellagrino G., Pigatto E., Lazzaroni M. -G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Guiducci S., Doria A., Salvarani C., Iannone F., Matucci-Cerinic M., Giorgio A., Alessia B., Francesca C., Renato C., Dall'Ara F., Angelo D. C., Marica D., Gianluca S., and Rossella T.

Abstract

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Published
2023

2. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology

Author

De Angelis R., Ferri C., Giuggioli D., Bajocchi G., Dagna L., Bellando-Randone S., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Lepri G., Girelli F., Riccieri V., Zanatta E., Bosello S. L., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A. M., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Cipolletta E., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Di Vico C., Gigante A., Pellagrino G., Pigatto E., Lazzaroni M. -G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Guiducci S., Doria A., Salvarani C., Iannone F., Matucci-Cerinic M., Giorgio A., Alessia B., Francesca C., Renato C., Dall'Ara F., Angelo D. C., Marica D., Gianluca S., Rossella T., De Angelis, R, Ferri, C, Giuggioli, D, Bajocchi, G, Dagna, L, Bellando-Randone, S, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Lepri, G, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Cipolletta, E, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Di Vico, C, Gigante, A, Pellagrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Guiducci, S, Doria, A, Salvarani, C, Iannone, F, Matucci-Cerinic, M, Giorgio, A, Alessia, B, Francesca, C, Renato, C, Dall'Ara, F, Angelo, D, Marica, D, Gianluca, S, Rossella, T, De Angelis, R., Ferri, C., Giuggioli, D., Bajocchi, G., Dagna, L., Bellando-Randone, S., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., Bosello, S. L., Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A. M., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Cipolletta, E., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Di Vico, C., Gigante, A., Pellagrino, G., Pigatto, E., Lazzaroni, M. -G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, G. D., Govoni, M., D'Angelo, S., Cozzi, F., Guiducci, S., Doria, A., Salvarani, C., Iannone, F., Matucci-Cerinic, M., Giorgio, A., Alessia, B., Francesca, C., Renato, C., Dall'Ara, F., Angelo, D. C., Marica, D., Gianluca, S., and Rossella, T.

Subjects
Scleroderma, Systemic, Settore MED/16 - REUMATOLOGIA, Epidemiology, Immunology, Systemic, Autoimmunity, Autoimmune Disease, Autoimmune Diseases, Scleroderma, Rheumatology, Immunology and Allergy, Seasons, Human
Abstract

ObjectiveTo describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.MethodsData involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.ResultsAmong patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (pConclusionThe ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Published
2023

3. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Author

Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., and Matucci-Cerinic M.

Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Published
2022

4. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri C., De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., and Ferri C.

Abstract

OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

5. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology

Author

De Angelis, R., Ferri, C., Giuggioli, D., Bajocchi, G., Dagna, L., Bellando-Randone, S., Zanframundo, G., Foti, Roberta, Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A. M., Ciano, G., Beretta, Carlo Luigi, Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Cipolletta, Eleonora, Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Di Vico, C., Gigante, A., Pellagrino, G., Pigatto, E., Lazzaroni, M. -G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, Maria Assunta, Carrara, Giancarlo, Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, Enrica Maria, Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Guiducci, S., Doria, A., Salvarani, C., Iannone, F., Matucci-Cerinic, M., Giorgio, A., Alessia, B., Francesca, C., Renato, C., Dall'Ara, F., Angelo, D. C., Marica, D., Gianluca, S., Rossella, T., Foti R., Bosello S. L. (ORCID:0000-0002-4837-447X), Beretta L. (ORCID:0000-0001-9924-2066), Cipolletta E., Zanetti A., Carrara G., Fusaro E., Sebastiani G. D., De Angelis, R., Ferri, C., Giuggioli, D., Bajocchi, G., Dagna, L., Bellando-Randone, S., Zanframundo, G., Foti, Roberta, Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A. M., Ciano, G., Beretta, Carlo Luigi, Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Cipolletta, Eleonora, Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Di Vico, C., Gigante, A., Pellagrino, G., Pigatto, E., Lazzaroni, M. -G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, Maria Assunta, Carrara, Giancarlo, Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, Enrica Maria, Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Guiducci, S., Doria, A., Salvarani, C., Iannone, F., Matucci-Cerinic, M., Giorgio, A., Alessia, B., Francesca, C., Renato, C., Dall'Ara, F., Angelo, D. C., Marica, D., Gianluca, S., Rossella, T., Foti R., Bosello S. L. (ORCID:0000-0002-4837-447X), Beretta L. (ORCID:0000-0001-9924-2066), Cipolletta E., Zanetti A., Carrara G., Fusaro E., and Sebastiani G. D.

Abstract

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Published
2023

6. One year in review 2021: novelties in the treatment of rheumatoid arthritis

Author

Silvagni, E., Garifallia Sakellariou, Bortoluzzi, A., Giollo, A., Ughi, N., Vultaggio, L., Scirè, C. A., Silvagni, E, Sakellariou, G, Bortoluzzi, A, Giollo, A, Ughi, N, Vultaggio, L, and Scire, C

Subjects
Disease-modifying anti-rheumatic drug, JAK inhibitors, SARS-CoV-2, Precision medicine, Immunology, COVID-19, Comorbidity, Biological agents, Disease-modifying anti-rheumatic drugs, Rheumatoid arthritis, NO, Arthritis, Rheumatoid, JAK inhibitor, Rheumatology, Antirheumatic Agents, Biological agent, Humans, Immunology and Allergy, Rheumatoid arthriti
Abstract

Management of rheumatoid arthritis (RA) has evolved over the years as a result of better understanding of the role of different therapeutic strategies, as well as following an increasing availability of new disease-modifying antirheumatic drugs. However, the role of patients in sharing decisions, as well as the rules informing precision medicine or the principles to follow in case of specific comorbidities or extra-articular manifestations are still areas for improvement. Moreover, in 2020, the novel Coronavirus disease-19 outbreak has completely changed many attitudes in terms of assessment and treatment paradigms in most clinical diseases, including RA. In this narrative review, the authors report their specific point of view on the management of RA, based on a critical revision of literature published in 2020, focusing on relevant novelties and future research directions.

Published
2021
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7. One year in review 2021: Novelties in the treatment of rheumatoid arthritis

Author

Silvagni, E, Sakellariou, G, Bortoluzzi, A, Giollo, A, Ughi, N, Vultaggio, L, Scire, C, Silvagni E., Sakellariou G., Bortoluzzi A., Giollo A., Ughi N., Vultaggio L., Scire C. A., Silvagni, E, Sakellariou, G, Bortoluzzi, A, Giollo, A, Ughi, N, Vultaggio, L, Scire, C, Silvagni E., Sakellariou G., Bortoluzzi A., Giollo A., Ughi N., Vultaggio L., and Scire C. A.

Abstract

Management of rheumatoid arthritis (RA) has evolved over the years as a result of better understanding of the role of different therapeutic strategies, as well as following an increasing availability of new disease-modifying antirheumatic drugs. However, the role of patients in sharing decisions, as well as the rules informing precision medicine or the principles to follow in case of specific comorbidities or extra-articular manifestations are still areas for improvement. Moreover, in 2020, the novel Coronavirus disease-19 outbreak has completely changed many attitudes in terms of assessment and treatment paradigms in most clinical diseases, including RA. In this narrative review, the authors report their specific point of view on the management of RA, based on a critical revision of literature published in 2020, focusing on relevant novelties and future research directions.

Published
2021

8. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), Sebastiani G. D., de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), and Sebastiani G. D.

Abstract

Objective. There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. Methods. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. Results. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

9. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Author

Ferri, C., De Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Lazzaroni, M. G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Bosello S. (ORCID:0000-0002-4837-447X), Sebastiani G. D., Ferri, C., De Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Lazzaroni, M. G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Bosello S. (ORCID:0000-0002-4837-447X), and Sebastiani G. D.

Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Published
2022

12. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

Rossella, De Angelis, Dilia, Giuggioli, Gianluigi, Bajocchi, Lorenzo, Dagna, Giovanni, Zanframundo, Rosario, Foti, Fabio, Cacciapaglia, Giovanna, Cuomo, Alarico, Ariani, Edoardo, Rosato, Serena, Guiducci, Francesco, Girelli, Valeria, Riccieri, Elisabetta, Zanatta, Silvia, Bosello, Ilaria, Cavazzana, Francesca, Ingegnoli, Maria De, Santis, Giuseppe, Murdaca, Giuseppina, Abignano, Nicoletta, Romeo, Alessandra, Della Rossa, Maurizio, Caminiti, Annamaria, Iuliano, Giovanni, Ciano, Lorenzo, Beretta, Gianluca, Bagnato, Ennio, Lubrano, Ilenia, De Andres, Alessandro, Giollo, Marta, Saracco, Cecilia, Agnes, Federica, Lumetti, Amelia, Spinella, Luca, Magnani, Corrado, Campochiaro, Giacomo, De Luca, Veronica, Codullo, Elisa, Visalli, Francesco, Masini, Antonietta, Gigante, Silvia, Bellando-Randone, Greta, Pellegrino, Erika, Pigatto, Francesca, Dall'Ara, Maria Grazia, Lazzaroni, Elena, Generali, Gianna, Mennillo, Simone, Barsotti, Giuseppa Pagano, Mariano, Francesca, Calabrese, Federica, Furini, Licia, Vultaggio, Simone, Parisi, Clara Lisa, Peroni, Anna Maria, Risa, Davide, Rozza, Anna, Zanetti, Greta, Carrara, Giampiero, Landolfi, Carlo Alberto, Scirè, Gerolamo, Bianchi, Enrico, Fusaro, Gian Domenico, Sebastiani, Marcello, Govoni, Salvatore, D'Angelo, Franco, Cozzi, Andrea, Doria, Florenzo, Iannone, Carlo, Salvarani, Marco, Matucci-Cerinic, Clodoveo, Ferri, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, S., Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, Giacomo., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, G. D., Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., De Angelis, Rossella, Giuggioli, Dilia, Bajocchi, Gianluigi, Dagna, Lorenzo, Zanframundo, Giovanni, Foti, Rosario, Cacciapaglia, Fabio, Cuomo, Giovanna, Ariani, Alarico, Rosato, Edoardo, Guiducci, Serena, Girelli, Francesco, Riccieri, Valeria, Zanatta, Elisabetta, Bosello, Silvia, Cavazzana, Ilaria, Ingegnoli, Francesca, De Santis, Maria, Murdaca, Giuseppe, Abignano, Giuseppina, Romeo, Nicoletta, Della Rossa, Alessandra, Caminiti, Maurizio, Iuliano, Annamaria, Ciano, Giovanni, Beretta, Lorenzo, Bagnato, Gianluca, Lubrano, Ennio, De Andres, Ilenia, Giollo, Alessandro, Saracco, Marta, Agnes, Cecilia, Lumetti, Federica, Spinella, Amelia, Magnani, Luca, Campochiaro, Corrado, De Luca, Giacomo, Codullo, Veronica, Visalli, Elisa, Masini, Francesco, Gigante, Antonietta, Bellando-Randone, Silvia, Pellegrino, Greta, Pigatto, Erika, Dall'Ara, Francesca, Lazzaroni, Maria Grazia, Generali, Elena, Mennillo, Gianna, Barsotti, Simone, Pagano Mariano, Giuseppa, Calabrese, Francesca, Furini, Federica, Vultaggio, Licia, Parisi, Simone, Peroni, Clara Lisa, Risa, Anna Maria, Rozza, Davide, Zanetti, Anna, Carrara, Greta, Landolfi, Giampiero, Scirè, Carlo Alberto, Bianchi, Gerolamo, Fusaro, Enrico, Sebastiani, Gian Domenico, Govoni, Marcello, D'Angelo, Salvatore, Cozzi, Franco, Doria, Andrea, Iannone, Florenzo, Salvarani, Carlo, Matucci-Cerinic, Marco, and Ferri, Clodoveo

Subjects
Male, medicine.medical_specialty, Vital capacity, Settore MED/16 - REUMATOLOGIA, Cross-sectional study, Immunology, Left, Socio-culturale, scleroderma, sex, systemic sclerosis, Disease, Ventricular Function, Left, Scleroderma, Systemic sclerosi, Rheumatology, Internal medicine, Sicca syndrome, Sex, Systemic sclerosis, Cross-Sectional Studies, Female, Humans, Italy, Registries, Sex Characteristics, Stroke Volume, Scleroderma, Systemic, Sjogren's Syndrome, medicine, LS8_2, Immunology and Allergy, Ventricular Function, Honeycombing, skin and connective tissue diseases, Ejection fraction, integumentary system, business.industry, Systemic, medicine.disease, Cohort, business
Abstract

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

13. Current Acquaintance on Agronomic Biofortification to Modulate the Yield and Functional Value of Vegetable Crops: A Review

Author

Beppe Benedetto Consentino, Michele Ciriello, Leo Sabatino, Lorena Vultaggio, Sara Baldassano, Sonya Vasto, Youssef Rouphael, Salvatore La Bella, Stefania De Pascale, Consentino, BB, Ciriello, M, Sabatino, L, Vultaggio, L, Baldassano, S, Vasto, S, Rouphael, Y, La Bella, S, and De Pascale, S

Subjects
mineral, trace elements, Plant Science, phytochemical, Horticulture, human diet
Abstract

Fresh vegetables and fruits have always been the mainstays of good nutrition as providers of fiber, beneficial phytochemicals (such as vitamins and phenolic compounds), and minerals. Today and in the future, biofortification is a promising strategy to increase the concentration of these compounds. Considering the importance of minerals in human health, the enrichment of fresh produce for consumption has been considered through specific agronomic approaches. This review discusses, in detail, the latest findings on vegetable agronomic biofortification, aimed at increasing the concentration of crucial minerals, such as iron (Fe), zinc (Zn), iodine (I), selenium (Se), molybdenum (Mo), and silicon (Si), in edible portions, focusing on the direct and indirect effects of this strategy. Although agronomic biofortification is considered a feasible technique, the approach is complex due to the many interactions between the microelement bioavailability for both plants and consumers. Therefore, the effects of biofortification on human health and the influence of beneficial and antinutritional compounds were discussed in detail to analyze the advantages and disadvantages of this practice.

Published
2023

14. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. the experience of the Italian SIR-SPRING registry and review of the world literature

Author

Clodoveo Ferri, Rossella De Angelis, Dilia Giuggioli, Gianluigi Bajocchi, Lorenzo Dagna, Giovanni Zanframundo, Rosario Foti, Fabio Cacciapaglia, Giovanna Cuomo, Alarico Ariani, Edoardo Rosato, Serena Guiducci, Francesco Girelli, Valeria Riccieri, Elisabetta Zanatta, Silvia Bosello, Ilaria Cavazzana, Francesca Ingegnoli, Maria De Santis, Giuseppe Murdaca, Giuseppina Abignano, Nicoletta Romeo, Alessandra Della Rossa, Maurizio Caminiti, Annamaria Iuliano, Giovanni Ciano, Lorenzo Beretta, Gianluca Bagnato, Ennio Lubrano, Ilenia De Andres, Alessandro Giollo, Marta Saracco, Cecilia Agnes, Federica Lumetti, Amelia Spinella, Luca Magnani, Corrado Campochiaro, Giacomo De Luca, Veronica Codullo, Elisa Visalli, Francesco Masini, Antonietta Gigante, Silvia Bellando-Randone, Greta Pellegrino, Erika Pigatto, Maria Grazia Lazzaroni, Franco Franceschini, Elena Generali, Gianna Mennillo, Simone Barsotti, Giuseppa Pagano Mariano, Francesca Calabrese, Federica Furini, Licia Vultaggio, Simone Parisi, Clara Lisa Peroni, Davide Rozza, Anna Zanetti, Greta Carrara, Giampiero Landolfi, Carlo Alberto Scirè, Gerolamo Bianchi, Enrico Fusaro, Gian Domenico Sebastiani, Marcello Govoni, Salvatore D'Angelo, Franco Cozzi, Andrea Doria, Florenzo Iannone, Carlo Salvarani, Marco Matucci-Cerinic, Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, and Matucci-Cerinic, M

Subjects
Settore MED/16 - REUMATOLOGIA, systemic sclerosis, Macro-areas, Immunology, Geographical areas, macro-areas, Antibodies, environmental, Environmental, Scleroderma, Tertiary Care Centers, Systemic sclerosi, Rheumatology, Antinuclear, Humans, Immunology and Allergy, scleroderma, Registries, Keywords: Environmental, Referral, Systemic sclerosis, Geographical area, Scleroderma, Systemic, geographical areas, Systemic, referral, Phenotype, Italy, Antibodies, Antinuclear, Macro-area
Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Published
2022

15. Iodine Biofortification and Seaweed Extract-Based Biostimulant Supply Interactively Drive the Yield, Quality, and Functional Traits in Strawberry Fruits

Author

Beppe Benedetto Consentino, Lorena Vultaggio, Nicolò Iacuzzi, Salvatore La Bella, Claudio De Pasquale, Youssef Rouphael, Georgia Ntatsi, Giuseppe Virga, Leo Sabatino, Consentino, B. B., Vultaggio, L., Iacuzzi, N., La Bella, S., De Pasquale, C., Rouphael, Y., Ntatsi, G., Virga, G., Sabatino, L., Consentino, Beppe Benedetto, Vultaggio, Lorena, Iacuzzi, Nicolò, La Bella, Salvatore, De Pasquale, Claudio, Rouphael, Youssef, Ntatsi, Georgia, Virga, Giuseppe, and Sabatino, Leo

Subjects
biofortification, stress tolerance, Ecology, biostimulants, algae extract, abiotic stress, Fragaria × ananassa, Plant Science, biostimulant, Ecology, Evolution, Behavior and Systematics, abiotic stre
Abstract

The horticultural sector is seeking innovative and sustainable agronomic practices which could lead to enhanced yield and product quality. Currently, plant biofortification is recognized as a valuable technique to improve microelement concentrations in plant tissues. Among trace elements, iodine (I) is an essential microelement for human nutrition. Concomitantly, the application of biostimulants may improve overall plant production and quality traits. With the above background in mind, an experiment was designed with the aim of assessing the interactive impact of a seaweed extract-based biostimulant (SwE) (0 mL L−1 (served as control) or 3 mL L−1 (optimal dosage)) and 0, 100, 300, or 600 mg L−1 I on the growth parameters, yield, fruit quality, minerals, and functional characteristics of the tunnel-grown “Savana” strawberry. SwE foliar application improved the plant growth-related traits, total and marketable yield, fruit color parameters, soluble solids content, nitrogen (N), potassium (K), and magnesium (Mg) fruit concentrations. Furthermore, an enhancement in the fruit dry matter content, ascorbic acid, and I concentration in fruits was detected when the SwE supply interacted with a mild I dose (100 or 300 mg L−1). The research underlined that combining SwE application and I biofortification increased the strawberry yield and quality and enhanced the plant nutritional status variation, thereby, determining a boosted strawberry I tolerance.

Published
2023
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16. Grafting Eggplant Onto Underutilized Solanum Species and Biostimulatory Action of Azospirillum brasilense Modulate Growth, Yield, NUE and Nutritional and Functional Traits

Author

Beppe Benedetto Consentino, Leo Sabatino, Lorena Vultaggio, Giuseppe Leonardo Rotino, Gaetano Giuseppe La Placa, Fabio D’Anna, Claudio Leto, Nicolò Iacuzzi, Claudio De Pasquale, Consentino B.B., Sabatino L., Vultaggio L., Rotino G.L., La Placa G.G., D'Anna F., Leto C., Iacuzzi N., and De Pasquale C.

Subjects
S. macrocarpon, S. aethiopicum, PGPB, S. torvum, Solanum melongena, microbial biostimulant, Settore AGR/04 - Orticoltura E Floricoltura, Plant Science, Horticulture
Abstract

The grafting of vegetable crops is considered a valuable mean for ensuring the yield and quality under different cultivation conditions. Simultaneously, there are increasing research efforts in exploiting underutilised plants as potential rootstocks for vegetables to increase the sustainability of horticultural systems. In accordance with the European Green Deal, the application of biostimulants is a fashionable and ecological agronomic practice to enhance the production and quality of vegetables. Thus, the current research appraised the synergistic effect of grafting eggplant onto various allied potential rootstocks (Solanum torvum, S. aethiopicum and S. macrocarpon) and of applying a plant growth-promoting bacteria (Azospirillum brasilense DSM 2298) on eggplant growth, production, fruit quality traits (nutritional and functional features) and nitrogen use efficiency (NUE). The findings showed that ‘Gloria’ F1 plants grafted onto S. torvum or S. aethiopicum had a significant increase in plant height 50 DAT by 11.6% and 9%, respectively, compared with not grafted plants. Simultaneously, plants inoculated with A. brasilense DSM 2298 acquired a significant upsurge of plant height 50 DAT by 6% compared with the control. Our results revealed that S. torvum and S. aethiopicum-grafted plants improved their marketable yield by 31.4% and 20%, respectively, compared with not grafted ones. Furthermore, A. brasilense DSM 2298 significantly boosted the yield compared with the control plants. Plant type had no effect on fruit dry matter and firmness, whereas plants grafted onto S. macrocarpon showed a significant increase in the soluble solids content (SSC) and fruit K concentration compared with not grafted plants. Plants grafted onto S. torvum rootstock and inoculated with A. brasilense DSM 2298 had a significant increase in fruit protein concentrations compared with the combination not grafted × control. Moreover, S. torvum-grafted plants and those inoculated with the microbial biostimulant revealed the highest NUE values. The results evidenced that S. torvum and S. macrocarpon-grafted plants, inoculated with A. brasilense DSM 2298, had the highest ascorbic acid (average 7.33 and 7.32 mg 100 g−1 fw, respectively). Interestingly, S. torvum rootstock increased the chlorogenic acid concentration and reduced the glycoalkaloids concentration compared with not grafted plants. Our data also showed that A. brasilense DSM 2298 significantly increased SSC by 4.5%, NUE by 5.5%, chlorogenic acid concentration by 2.0% and the total anthocyanins by 0.2% compared to the control. Thus, our study underlined that S. aethiopicum rootstocks inoculated with A. brasilense DSM 2298 could represent a valid substitute to the common S. torvum rootstock.

Published
2022
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17. Single or Blended Application of Non-Microbial Plant-Based Biostimulants and Trichoderma atroviride as a New Strategy to Enhance Greenhouse Cherry Tomato Performance.

Author

Vultaggio L, Ciriello M, Campana E, Bellitto P, Consentino BB, Rouphael Y, Colla G, Mancuso F, La Bella S, Napoli S, and Sabatino L

Abstract

The need to increase yield and enhance the sustainability of crop production systems has led to the development and employment of natural products, such as plant biostimulants. In recent years, a number of reports have researched the effects of biostimulants on plant performance; however, few studies have focused on the mutual application of microbial and/or non-microbial biostimulants. This research, conducted in the framework of the SO.MI.PR.O.N regional project, aimed to investigate the single or mutual application of three biostimulants, a tropical plant extract (PE), a vegetal protein hydrolysate (PH), and Trichoderma atroviride , on 'Creativo' F1 cherry tomato plants cultivated during two growing cycles (2022-2023 and 2023-2024). Our results showed that plants treated with the combination Tricho + PE + PH had statistically significant higher fresh shoot biomass (+64.2%, 1647.0 g plant -1 ), total fruit production (+37.9%, 1902.5 g plant -1 ), marketable fruit production (+52.9%, 1778.5 g plant -1 ), and average weight of marketable fruits (+53.1%, 17.0 g) compared to control plants (untreated plants). Furthermore, biostimulant treatments, especially T. atroviride , variably enhanced cherry tomato fruits' qualitative traits, such as firmness, total soluble solids, ascorbic acid, lycopene, and total polyphenols compared to control plants. Overall, the best combinations to increase tomato fruit qualitative features were PE + PH, Tricho + PE, and Tricho + PH. From an economic point of view, the best treatment for achieving the highest net return was PE. This study underlines that biostimulant features (yield, qualitative aspects, and economic profitability) can be supported through the application of specific biostimulant combinations.

Published
2024
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18. Modulation of cherry tomato performances in response to molybdenum biofortification and arbuscular mycorrhizal fungi in a soilless system.

Author

Vultaggio L, Allevato E, Sabatino L, Ntatsi G, Rouphael Y, Torta L, La Bella S, and Consentino BB

Abstract

Molybdenum (Mo) is a crucial microelement for both, humans and plants. The use of agronomic biofortification techniques can be an alternative method to enhance Mo content in vegetables. Concomitantly, arbuscular mycorrhizal fungi (AMF) application is a valuable strategy to enhance plant performances and overcome plant abiotic distresses such as microelement overdose. The aim of this research was to estimate the direct and/or indirect effects of Mo supply at four doses [0.0, 0.5 (standard dose), 2.0 or 4.0 μmol L -1 ], alone or combined with AMF inoculation, on plant performances. In particular, plant height and first flower truss emission, productive features (total yield, marketable yield and average marketable fruit weight) and fruit qualitative characteristics (fruit dry matter, soluble solids content, titratable acidity, ascorbic acid, lycopene, polyphenol, nitrogen, copper, iron and molybdenum) of an established cherry tomato genotype cultivated in soilless conditions were investigated. Moreover, proline and malondialdehyde concentrations, as well as Mo hazard quotient (HQ) in response to experimental treatments were determined. A split-plot randomized experimental block design with Mo dosages as plots and +AMF or -AMF as sub-plots was adopted. Data revealed that AMF inoculation enhanced marketable yield (+50.0 %), as well as some qualitative traits, such as fruit soluble solids content (SSC) (+9.9 %), ascorbic acid (+7.3 %), polyphenols (+2.3 %), and lycopene (+2.5 %). Molybdenum application significantly increased SSC, polyphenols, fruit Mo concentration (+29.0 % and +100.0 % in plants biofortified with 2.0 and 4.0 μmol Mo L -1 compared to those fertigated with the standard dose, respectively) and proline, whereas it decreased N (-25.0 % and -41.6 % in plants biofortified with 2.0 and 4.0 μmol Mo L -1 compared to those fertigated with the standard dose, respectively). Interestingly, the application of AMF mitigated the detrimental effect of high Mo dosages (2.0 or 4.0 μmol L -1 ). A pronounced advance in terms of plant height 45 DAT, fruit lycopene concentration and fruit Fe, Cu and Mo concentrations was observed when AMF treatment and Mo dosages (2.0 or 4.0 μmol Mo L -1 ) were combined. Plants inoculated or not with AMF showed an improvement in the hazard quotient (HQ) in reaction to Mo application. However, the HQ - for a consumption of 200 g day -1 of biofortified cherry tomato - remained within the safety level for human consumption. This study suggests that Mo-implementation (at 2.0 or 4.0 μmol L -1 ) combined with AMF inoculation could represent a viable cultivation protocol to enhance yield, produce premium quality tomato fruits and, concomitantly, improve Mo dose in human diet. In the light of our findings, further studies on the interaction between AMF and microelements in other vegetable crops are recommended., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Published
2024
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19. Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.

Author

Riccieri V, Pellegrino G, Cipolletta E, Giuggioli D, Bajocchi G, Bellando-Randone S, Dagna L, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Lepri G, Girelli F, Zanatta E, Bosello SL, Cavazzana I, Ingegnoli F, De Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano A, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Di Vico C, Gigante A, Saccon F, Grazia Lazzaroni M, Franceschini F, Generali E, Mennillo G, Barsotti S, Pagano Mariano G, Calabrese F, Furini F, Vultaggio L, Parisi S, Peroni CL, Bianchi G, Conti F, Cozzi F, D'Angelo S, Doria A, Fusaro E, Govoni M, Guiducci S, Iannone F, Salvarani C, Sebastiani GD, Ferri C, Matucci-Cerinic M, and De Angelis R

Abstract

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data., Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group)., Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, " late " scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis., Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Published
2024
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20. Boosting plant food polyphenol concentration by saline eustress as supplement strategies for the prevention of metabolic syndrome: an example of randomized interventional trial in the adult population.

Author

Ferrantelli V, Vasto S, Alongi A, Sabatino L, Baldassano D, Caldarella R, Gagliano R, Di Rosa L, Consentino BB, Vultaggio L, and Baldassano S

Abstract

Introduction: Phenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism., Methods: Forty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition., Results: Salinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected., Discussion: Supplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected., Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Ferrantelli, Vasto, Alongi, Sabatino, Baldassano, Caldarella, Gagliano, Di Rosa, Consentino, Vultaggio and Baldassano.)

Published
2023
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21. Development of a New Micropropagation Protocol and Transfer of In Vitro Plants to In Vivo Conditions for Cascade Hop.

Author

Iacuzzi N, Salamone F, Farruggia D, Tortorici N, Vultaggio L, and Tuttolomondo T

Abstract

The vegetative propagation of hops, despite being a reliable method, is not very common due to the unavailability of the plant material. In this study, the technique of in vitro propagation was applied to the Cascade variety of Humulus lupulus L. The plant material was collected from a private field in Sicily; the explants were subjected to sterilization before in vitro culture. Single-node explants were placed in in vitro culture in nine different culture media for multiplication. Thidiazuron (TDZ), Benzyladenine (BAP) and meta-Topoline (mT) were tested for multiplication phase. For the rooting phase, five types of different culture media were evaluated. Binodal cuttings coming from the previous multiplication test were placed in the culture. The rooting media differ from each other in the concentration and ratio of two auxin hormones: Indolo-3-acetic acid (IAA) and Indole-3-butyric acid (IBA). In vitro rooted plants obtained from the rooting phase were transferred to ex vitro conditions in a microbox with agri-perlite and a solution containing Murashige and Skoog (MS) basal medium at half concentration. With a culture medium containing the highest TDZ doses (H6) and combination with cytokinin (H8 and H9), the highest shoot percentage was obtained. After 3 months of in vitro culture, the highest shoot percentage was observed in the culture medium with 2 mL L -1 of BAP. The highest rooting percentage, roots numbers and root length were found when the culture medium was supplemented with 1 mL L -1 of IAA. The usage of agri-perlite and MS at half concentration, without PGR, allowed us to obtain a 99.1% survival rate. This micropropagation protocol is useful for obtaining virus-free plants and for the development of the brewery industry.

Published
2023
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22. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology.

Author

De Angelis R, Ferri C, Giuggioli D, Bajocchi G, Dagna L, Bellando-Randone S, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Lepri G, Girelli F, Riccieri V, Zanatta E, Bosello SL, Cavazzana I, Ingegnoli F, De Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano AM, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Cipolletta E, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Di Vico C, Gigante A, Pellagrino G, Pigatto E, Lazzaroni MG, Franceschini F, Generali E, Mennillo G, Barsotti S, Mariano GP, Furini F, Vultaggio L, Parisi S, Peroni CL, Rozza D, Zanetti A, Carrara G, Landolfi G, Scirè CA, Bianchi G, Fusaro E, Sebastiani GD, Govoni M, D'Angelo S, Cozzi F, Guiducci S, Doria A, Salvarani C, Iannone F, and Matucci-Cerinic M

Subjects
Humans, Seasons, Rheumatology, Scleroderma, Systemic, Autoimmune Diseases
Abstract

Objective: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort., Methods: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets., Results: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001)., Conclusion: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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23. Iodine Biofortification and Seaweed Extract-Based Biostimulant Supply Interactively Drive the Yield, Quality, and Functional Traits in Strawberry Fruits.

Author

Consentino BB, Vultaggio L, Iacuzzi N, La Bella S, De Pasquale C, Rouphael Y, Ntatsi G, Virga G, and Sabatino L

Abstract

The horticultural sector is seeking innovative and sustainable agronomic practices which could lead to enhanced yield and product quality. Currently, plant biofortification is recognized as a valuable technique to improve microelement concentrations in plant tissues. Among trace elements, iodine (I) is an essential microelement for human nutrition. Concomitantly, the application of biostimulants may improve overall plant production and quality traits. With the above background in mind, an experiment was designed with the aim of assessing the interactive impact of a seaweed extract-based biostimulant (SwE) (0 mL L -1 (served as control) or 3 mL L -1 (optimal dosage)) and 0, 100, 300, or 600 mg L -1 I on the growth parameters, yield, fruit quality, minerals, and functional characteristics of the tunnel-grown "Savana" strawberry. SwE foliar application improved the plant growth-related traits, total and marketable yield, fruit color parameters, soluble solids content, nitrogen (N), potassium (K), and magnesium (Mg) fruit concentrations. Furthermore, an enhancement in the fruit dry matter content, ascorbic acid, and I concentration in fruits was detected when the SwE supply interacted with a mild I dose (100 or 300 mg L -1 ). The research underlined that combining SwE application and I biofortification increased the strawberry yield and quality and enhanced the plant nutritional status variation, thereby, determining a boosted strawberry I tolerance.

Published
2023
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24. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature.

Author

Ferri C, De Angelis R, Giuggioli D, Bajocchi G, Dagna L, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Guiducci S, Girelli F, Riccieri V, Zanatta E, Bosello S, Cavazzana I, Ingegnoli F, De Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano A, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Masini F, Gigante A, Bellando-Randone S, Pellegrino G, Pigatto E, Lazzaroni MG, Franceschini F, Generali E, Mennillo G, Barsotti S, Mariano GP, Calabrese F, Furini F, Vultaggio L, Parisi S, Peroni CL, Rozza D, Zanetti A, Carrara G, Landolfi G, Scirè CA, Bianchi G, Fusaro E, Sebastiani GD, Govoni M, D'Angelo S, Cozzi F, Doria A, Iannone F, Salvarani C, and Matucci-Cerinic M

Subjects
Antibodies, Antinuclear, Humans, Italy epidemiology, Phenotype, Registries, Tertiary Care Centers, Rheumatology, Scleroderma, Systemic diagnosis
Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature., Materials and Methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas., Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches., Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Published
2022
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25. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology.

Author

De Angelis R, Giuggioli D, Bajocchi G, Dagna L, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Guiducci S, Girelli F, Riccieri V, Zanatta E, Bosello S, Cavazzana I, Ingegnoli F, Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano A, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Masini F, Gigante A, Bellando-Randone S, Pellegrino G, Pigatto E, Dall'Ara F, Lazzaroni MG, Generali E, Mennillo G, Barsotti S, Mariano GP, Calabrese F, Furini F, Vultaggio L, Parisi S, Peroni CL, Risa AM, Rozza D, Zanetti A, Carrara G, Landolfi G, Scirè CA, Bianchi G, Fusaro E, Sebastiani GD, Govoni M, D'Angelo S, Cozzi F, Doria A, Iannone F, Salvarani C, Matucci-Cerinic M, and Ferri C

Subjects
Cross-Sectional Studies, Female, Humans, Italy epidemiology, Male, Registries, Sex Characteristics, Stroke Volume, Ventricular Function, Left, Rheumatology, Scleroderma, Systemic diagnosis, Sjogren's Syndrome
Abstract

Objective: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics., Methods: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared., Results: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs., Conclusion: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex., (© 2022 by the Journal of Rheumatology.)

Published
2022
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