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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. 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

7. 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

8. Effects of the dual hypocretin/orexin receptor antagonist Suvorexant on sleep and maternal behavior in lactating rats

Author: Rivas, M., Peña, F., Carrera-Cañas, C., Carrasco, B., Ferreira, A., Torterolo, P., De Andrés, I., Garzón, M., and Benedetto, L.
Published: 2024
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9. Acute effects of suvorexant on the proportions and architecture of the sleep-wake cycle stages in wild-type rats: induction of narcoleptic traits

Author: Carrera-Cañas, C., Rivas, M., Callejo, M., De Andrés, I., Torterolo, P., and Garzón, M.
Published: 2024
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10. AB0564 HEART VALVULAR ALTERATIONS IN A MULTICENTRE ITALIAN COHORT OF SSC PATIENTS

Author: Colaci, M., primary, Schinocca, C., additional, Dal Bosco, Y., additional, Aprile, M. L., additional, Guggino, G., additional, De Andres, I., additional, Russo, A. A., additional, Sambataro, D., additional, Sambataro, G., additional, and Malatino, L., additional
Published: 2020
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11. AB0563 AORTIC ROOT DILATION IN ASSOCIATED WITH THE REDUCTION OF CAPILLARY DENSITY OBSERVED AT NAILFOLD CAPILLAROSCOPY IN SSC PATIENTS

Author: Colaci, M., primary, Dal Bosco, Y., additional, Schinocca, C., additional, Aprile, M. L., additional, Guggino, G., additional, De Andres, I., additional, Russo, A. A., additional, Sambataro, G., additional, Sambataro, D., additional, and Malatino, L., additional
Published: 2020
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12. Reliability of a Competitive Enzyme-linked Immunosorbent Assay (ELISA) in Detection of Narcolepsy

Author: Carrera-Cañas, C., Del Río-Villegas, R., Ojeda, J., Callejo, M., Garzón, M., and De Andrés, I.
Published: 2022
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13. New narcolepsy-ataxia and neuropathy phenotype not associated with DNMT1

Author: Navarrete Pérez, J.J., Ojerda, J., Carrera-Cañas, C., Callejo, M., Sanz, R., de Andrés, I., Garzón, M., and del Rio-Villegas, R.
Published: 2022
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14. Hypocretin Release and Plasticity of Hypocretinergic Receptors in a Pharmacological Model with Narcolepsy-like Features Induced by Suvorexant in Rats

Author: Carrera-Cañas, C., Garzón, M., Callejo, M., and De Andrés, I.
Published: 2022
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15. 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: Carlo Alberto Scirè, Andrea Doria, Marcello Govoni, Gerolamo Bianchi, Marco Matucci-Cerinic, Florenzo Iannone, Ennio Lubrano, Corrado Campochiaro, Veronica Codullo, Alessandra Della Rossa, Gemma Lepri, Elisabetta Zanatta, Beretta Lorenzo, Doria Andrea, Lepri Gemma, Lorenzo Beretta, Greta Carrara, Alarico Ariani, Simone Parisi, Marta Saracco, Francesco Girelli, Maria De Santis, Federica Lumetti, Dilia Giuggioli, Enrico Fusaro, Simone Barsotti, Ilaria Cavazzana, Federica Furini, Carlo Salvarani, Serena Guiducci, Franco Cozzi, Valeria Riccieri, Francesca Ingegnoli, Edoardo Rosato, Antonietta Gigante, Rosario Foti, Elisa Visalli, Fabio Cacciapaglia, Lorenzo Dagna, Franco Franceschini, Silvia Bellando-Randone, Giovanna Cuomo, Gianluigi Bajocchi, Alessandro Giollo, Giacomo De Luca, Giuseppina Abignano, Carlo Sciré, Anna Zanetti, Giovanni Zanframundo, Edoardo Cipolletta, Silvia Laura Bosello, Clodoveo Ferri, Amelia Spinella, Giuseppa Pagano Mariano, Maurizio Caminiti, Giuseppe Murdaca, Salvatore D'Angelo, Gianpiero Landolfi, Nicoletta Romeo, Gian Domenico Sebastiani, Erika Pigatto, Rossella De Angelis, Davide Rozza, Maria-Grazia Lazzaroni, Anna Maria Iuliano, Giovanni Ciano, Gianluca Bagnato, Ilenia De Andres, Cecilia Agnes, Luca Magnani, Claudio Di Vico, Greta Pellagrino, Elena Generali, Gianna Mennillo, Licia Vultaggio, Clara Lisa Peroni, Abignano Giuseppina, Agnes Cecilia, Amato Giorgio, Ariani Alarico, Bagnato Gianluca, Bajoicchi Gianluigi, Barsotti Simone, Bellando-Randone Silvia, Benenati Alessia, Bianchi Gerolamo, Bosello Silvia, Cacciapaglia Fabio, Calabrese Francesca, Caminiti Maurizio, Campochiaro Corrado, Carignola Renato, Ciano Giovanni, Cipolletta Edoardo, Codullo Veronica, Cozzi Franco, Cuomo Giovanna, D’Angelo Salvatore, Dagna Lorenzo, Dall’Ara Francesca, De Andres Ilenia, De Angelis Rossella, De Cata Angelo, De Luca Giacomo, De Santis Maria, Della Rossa Alessandra, Di Vico Claudio, Doveri Marica, Foti Rosario, Furini Federica, Fusaro Enrico, Generali Elena, Gigante Antonietta, Giollo Alessandro, Girelli Francesco, Giuggioli Dilia, Govoni Marcello, Guiducci Serena, Iannone Florenzo, Ingegnoli Francesca, Iuliano Anna Maria, Lazzaroni Maria Grazia, Lubrano Ennio, Lumetti Federica, Magnani Luca, Mennillo Gianna, Murdaca Giuseppe Ospedale, Pagano Mariano Giuseppa, Parisi Simone, Pellegrino Greta, Peroni Clara Lisa, Pigatto Erika, Riccieri Valeria, Romeo Nicoletta, Rosato Edoardo, Sambataro Gianluca, Saracco Marta, Sebastiani Giandomenico, Spinella Amelia, Talotta Rossella, Visalli Elisa, Vultaggio Licia, Zanatta Elisabetta, and Zanframundo Giovanni
Subjects: Medicine
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
Published: 2023
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16. AB0329 Ultrasound 7 versus Ultrasound12 in Monitoring The Response To Adalimumab in Patients with Rheumatoid Arthritis

Author: Tropea, S., primary, De Andres, I., additional, Santonocito, P., additional, Russo, A.A., additional, and Battaglia, E., additional
Published: 2016
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17. Pain Intensity and Threshold in Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis Patients: Correlations with the Hamilton Depression Rating Scale

Author: Bagnato, Gianfilippo, Atteritano, Marco, Sorbara, S., De Andres, I., Talotta, R., Corallo, G., Verduci, E., Miceli, G., Sangari, D., Visalli, E., Marino, N., Morgante, S., Roberts, W. N., and Bagnato, Gianluca
Published: 2013

18. CHRONIC PAIN AND DEPRESSION: PAIN THRESHOLD AND VISUAL ANALOGUE SCALE

Author: Bagnato, Gianfilippo, Atteritano, Marco, De Andres, I., Talotta, R., Sangari, D., Miceli, G., and Bagnato, Gianluca
Published: 2012

19. effetti protettivi del colecalciferolo sull'attività di malattia in pazienti affetto da artrite reumatoide: dati a 12 mesi

Author: Atteritano, Marco, Tamburello, A., Miceli, G., Sangari, D., Bagnato, Gianfilippo, Lo Gullo, R., Sorbara, S., De Andres, I., Morgante, S., and Bagnato, Gianluca
Published: 2011

20. SAT0629 Diagnostic Performance of High Resolution Trans-Thotacic Lung Ultrasonography in Pulmonary Involvement of Connective Lung Disease in Treatment with Cyclophosphamide

Author: Tropea, S., primary, Bentivegna, M., additional, De Andres, I., additional, Russo, A., additional, Santonocito, P., additional, and Battaglia, E., additional
Published: 2015
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21. Hypocretin/Orexin Neuropeptides: Participation in the Control of Sleep- Wakefulness Cycle and Energy Homeostasis

Author: Nunez, A., primary, Rodrigo-Angulo, M., additional, De Andres, I., additional, and Garzon, M., additional
Published: 2009
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22. Chronic neuropathy with IgM anti-ganglioside antibodies: Lack of long term response to rituximab

Author: Rojas-Garcia, R., primary, Gallardo, E., additional, de Andres, I., additional, de Luna, N., additional, Juarez, C., additional, Sanchez, P., additional, and Illa, I., additional
Published: 2003
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23. The absence of survival motor neuron 2 gene may play a role in multifocal motor neuropathy

Author: Rojas-Garcia, R., primary, Tizzano, E., additional, Cusco, I., additional, Gallardo, E., additional, Barcelo, M. J., additional, de Andres, I., additional, Larrode, P., additional, Marti-Masso, J. F., additional, Martinez-Matos, J. A., additional, Povedano, M., additional, Rallo, B., additional, Serrano, S., additional, Baiget, M., additional, and Illa, I., additional
Published: 2002
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24. Histamine interaction with the ventral part of the oral pontine tegmentum: its implication in rem sleep modulation

Author: Bódalo, C. and De Andrés, I.
Published: 2013
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25. Cortical Visual Evoked Potentials During the Sleep-Wakefulness Cycle in the Freely Moving Cat. A Dynamic Study

Author: Siguenza, J. A., De Andres, I., Ibarz, J. M., and Reinoso-suarez, F.
Abstract: The dynamic features of visual evoked potentials, elicited by a light emitting diode chronically implanted in the frontal sinus of the freely moving cat, were studied during sleep stages by means of calculation of the power spectra of the EEG prior to the stimulus and the poststimulus EEG which contain the single evoked potential. The statistical analysis between mean frequencies from both EEG prior to the stimulus and single evoked potential, within each sleep stage, showed that the main changes occurred during slow sleep, with a significant increase in the percentage of the alpha band. These results are interpreted as a partial desynchronization evoked by the visual stimulation during the synchronized phase of sleep.
Published: 1985
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26. Cortical visual evoked potentials during the sleep wakefulness cycle of the freely moving cat. Characterization and statistical comparisons

Author: Sigüenza, J.A, primary, De Andres, I, additional, Ibarz, J.M, additional, and Reinoso-Suarez, F, additional
Published: 1984
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27. 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

28. Opiate microinjections in the locus coeruleus area of the cat enhance slow wave sleep

Author: Garzón, M, Tejero, S, Benéitez, A.M, and de Andrés, I
Published: 1995
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29. Unilateral lesions in locus coeruleus area enhance paradoxical sleep

Author: Caballero, A and De Andrés, I
Published: 1986
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30. Participation of the cerebellum in the regulation of the sleep-wakefulness cycle. Results in cerebellectomized cats

Author: Cunchillos, J.D and De Andrés, I
Published: 1982
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31. 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

32. Aortic root dilation in associated with the reduction in capillary density observed at nailfold capillaroscopy in SSc patients

Author: Ilenia De Andres, Ylenia Dal Bosco, Giuseppe Ronsivalle, A. A. Russo, Domenico Sambataro, Lorenzo Malatino, C. Schinocca, Giuliana Guggino, Michele Colaci, Gianluca Sambataro, Colaci M., Dal Bosco Y., Schinocca C., Ronsivalle G., Guggino G., De Andres I., Russo A.A., Sambataro D., Sambataro G., and Malatino L.
Subjects: Adult, medicine.medical_specialty, Vasa vasorum, Microscopic Angioscopy, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Medicine, Aortic root, Humans, 030212 general & internal medicine, Endothelial dysfunction, Nailfold Capillaroscopy, Videocapillaroscopy, Aged, 030203 arthritis & rheumatology, Autoimmune disease, Scleroderma, Systemic, integumentary system, business.industry, Microangiopathy, General Medicine, Middle Aged, medicine.disease, Dilatation, Capillaries, medicine.anatomical_structure, Capillary density, Nails, Cardiology, Systemic sclerosis, business, Aortic root dilation
Abstract: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibroblasts activation. Microvascular disease may be easily observed by means of nailfold capillaroscopy. Recent evidences emphasized also the involvement of large-medium arteries in SSc, mainly in terms of increased stiffness of the vessel wall. The study aims to measure aortic root diameter in a cohort of SSc patients and to correlate echocardiographic findings with the capillaroscopic pictures. We analyzed the clinical records of 125 consecutive SSc patients (M/F 14/111, mean age 55 ± 12.7years, median disease duration 11years) referring in 3 second-level rheumatology centers. All subjects underwent to heart ultrasound evaluation and videocapillaroscopic evaluation. At capillaroscopy, the patients with early SSc pattern belonged to the subgroup 1, while those with the active/late patterns (characterized by the reduction of capillary density) belonged to the subgroup 2. We found aortic root dilation in 8 (6.4%) SSc patients, with a mean value of 37.8 ± 1.2mm (range 37–40mm). Aortic root dilation was observed in only one patient in the subgroup 1 (1/62, 1.6%) and in 7 cases of the subgroup 2 (7/63, 11.1%; p = 0.03). Our study found a significant association between aortic root dilation and impairment of capillary density at nailfold videocapillaroscopy in SSc patients. We hypothesize that SSc-related microangiopathy revealed by nailfold videocapillaroscopy could mimic that of aortic vasa vasorum, contributing to deteriorate the aortic wall structure and favoring aortic root dilation and stiffening.
Published: 2021

33. Heart Valve Abnormalities in Systemic Sclerosis Patients; A Multicenter Cohort Study and Review of the Literature

Author: Domenico Sambataro, A. A. Russo, Giuseppe Ronsivalle, Michele Colaci, Gianluca Sambataro, Giuliana Guggino, Ylenia Dal Bosco, Lorenzo Malatino, C. Schinocca, Ilenia De Andres, Colaci M., Schinocca C., Dal Bosco Y., Ronsivalle G., Guggino G., De Andres I., A. Russo S., Sambataro D., Sambataro G., and Malatino L.
Subjects: Aortic valve, Adult, Male, medicine.medical_specialty, Heart Valve Diseases, Tricuspid stenosis, Scleroderma, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Tricuspid Valve Insufficiency, Mitral, Internal medicine, Medicine, Humans, Multicenter Studies as Topic, cardiovascular diseases, 030212 general & internal medicine, Heart valve, skin and connective tissue diseases, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, integumentary system, business.industry, Systemic, Mitral Valve Insufficiency, Middle Aged, medicine.disease, Valvular disease, Heart Valves, Stenosis, medicine.anatomical_structure, Pulmonary valve, cardiovascular system, Cardiology, Systemic sclerosis, Female, business, Tricuspid, Cohort study
Abstract: Background Systemic sclerosis (SSc) is a chronic autoimmune disease that is characterized by vasculopathy and fibrosis of the skin and visceral organs. Heart valve diseases are poorly described and generally not considered typical of SSc. We aimed to describe valvular abnormalities in a multicenter cohort of SSc patients and to investigate their correlation with SSc features. Methods We recruited 118 consecutive SSc patients (male/female, 14/104; mean age, 55.2 ± 12.1 years) in 3 rheumatology centers in Sicily, Italy, from January to October 2019. Results Mitral and tricuspid valve insufficiency was found in 85% and 91% of patients, respectively; regurgitations were generally mild and never severe. Mitral stenosis was rare (2%), and tricuspid stenosis was not observed. Sclerosis and calcification were present in 30% of mitral valves and in only 4% of tricuspid valves. The aortic valve was affected in 25% of cases, and it generally presented as regurgitation or sclerosis, whereas stenosis was rare (3%). Finally, 11% of SSc patients showed regurgitation of the pulmonary valve. No specific associations between SSc features and valve alterations were found. Conclusions Valvular diseases are frequently observed in SSc patients, with a predominant pattern of valvular regurgitations. Therefore, echocardiography should be routinely performed during SSc patient follow-up, considering the potential influence of additional cardiac involvement in the prognosis of these patients.
Published: 2020

34. 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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35. The ribosome quality control factor Asc1 determines the fate of HSP70 mRNA on and off the ribosome.

Author: Alagar Boopathy LR, Beadle E, Xiao AR, Garcia-Bueno Rico A, Alecki C, Garcia de-Andres I, Edelmeier K, Lazzari L, Amiri M, and Vera M
Subjects: RNA, Messenger genetics, RNA, Messenger metabolism, Ribosomes genetics, Ribosomes metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, HSP70 Heat-Shock Proteins genetics, HSP70 Heat-Shock Proteins metabolism, Codon metabolism, Protein Biosynthesis, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism
Abstract: Cells survive harsh environmental conditions by potently upregulating molecular chaperones such as heat shock proteins (HSPs), particularly the inducible members of the HSP70 family. The life cycle of HSP70 mRNA in the cytoplasm is unique-it is translated during stress when most cellular mRNA translation is repressed and rapidly degraded upon recovery. Contrary to its 5' untranslated region's role in maximizing translation, we discovered that the HSP70 coding sequence (CDS) suppresses its translation via the ribosome quality control (RQC) mechanism. The CDS of the most inducible Saccharomyces cerevisiae HSP70 gene, SSA4, is uniquely enriched with low-frequency codons that promote ribosome stalling during heat stress. Stalled ribosomes are recognized by the RQC components Asc1p and Hel2p and two novel RQC components, the ribosomal proteins Rps28Ap and Rps19Bp. Surprisingly, RQC does not signal SSA4 mRNA degradation via No-Go-Decay. Instead, Asc1p destabilizes SSA4 mRNA during recovery from heat stress by a mechanism independent of ribosome binding and SSA4 codon optimality. Therefore, Asc1p operates in two pathways that converge to regulate the SSA4 mRNA life cycle during stress and recovery. Our research identifies Asc1p as a critical regulator of the stress response and RQC as the mechanism tuning HSP70 synthesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Published: 2023
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36. 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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37. 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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38. 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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39. Heart Valve Abnormalities in Systemic Sclerosis Patients: A Multicenter Cohort Study and Review of the Literature.

Author: Colaci M, Schinocca C, Bosco YD, Ronsivalle G, Guggino G, de Andres I, Russo AA, Sambataro D, Sambataro G, and Malatino L
Subjects: Adult, Aged, Cohort Studies, Female, Heart Valves diagnostic imaging, Humans, Male, Middle Aged, Multicenter Studies as Topic, Heart Valve Diseases diagnosis, Heart Valve Diseases epidemiology, Heart Valve Diseases etiology, Mitral Valve Insufficiency, Scleroderma, Systemic complications, Scleroderma, Systemic diagnosis, Scleroderma, Systemic epidemiology, Tricuspid Valve Insufficiency diagnosis, Tricuspid Valve Insufficiency epidemiology, Tricuspid Valve Insufficiency etiology
Abstract: Background: Systemic sclerosis (SSc) is a chronic autoimmune disease that is characterized by vasculopathy and fibrosis of the skin and visceral organs. Heart valve diseases are poorly described and generally not considered typical of SSc. We aimed to describe valvular abnormalities in a multicenter cohort of SSc patients and to investigate their correlation with SSc features., Methods: We recruited 118 consecutive SSc patients (male/female, 14/104; mean age, 55.2 ± 12.1 years) in 3 rheumatology centers in Sicily, Italy, from January to October 2019., Results: Mitral and tricuspid valve insufficiency was found in 85% and 91% of patients, respectively; regurgitations were generally mild and never severe. Mitral stenosis was rare (2%), and tricuspid stenosis was not observed. Sclerosis and calcification were present in 30% of mitral valves and in only 4% of tricuspid valves. The aortic valve was affected in 25% of cases, and it generally presented as regurgitation or sclerosis, whereas stenosis was rare (3%). Finally, 11% of SSc patients showed regurgitation of the pulmonary valve. No specific associations between SSc features and valve alterations were found., Conclusions: Valvular diseases are frequently observed in SSc patients, with a predominant pattern of valvular regurgitations. Therefore, echocardiography should be routinely performed during SSc patient follow-up, considering the potential influence of additional cardiac involvement in the prognosis of these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2022
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40. Aortic root dilation in associated with the reduction in capillary density observed at nailfold capillaroscopy in SSc patients.

Author: Colaci M, Dal Bosco Y, Schinocca C, Ronsivalle G, Guggino G, De Andres I, Russo AA, Sambataro D, Sambataro G, and Malatino L
Subjects: Adult, Aged, Capillaries diagnostic imaging, Dilatation, Humans, Middle Aged, Nails diagnostic imaging, Microscopic Angioscopy, Scleroderma, Systemic diagnostic imaging
Abstract: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibroblasts activation. Microvascular disease may be easily observed by means of nailfold capillaroscopy. Recent evidences emphasized also the involvement of large-medium arteries in SSc, mainly in terms of increased stiffness of the vessel wall. The study aims to measure aortic root diameter in a cohort of SSc patients and to correlate echocardiographic findings with the capillaroscopic pictures. We analyzed the clinical records of 125 consecutive SSc patients (M/F 14/111, mean age 55 ± 12.7 years, median disease duration 11 years) referring in 3 second-level rheumatology centers. All subjects underwent to heart ultrasound evaluation and videocapillaroscopic evaluation. At capillaroscopy, the patients with early SSc pattern belonged to the subgroup 1, while those with the active/late patterns (characterized by the reduction of capillary density) belonged to the subgroup 2. We found aortic root dilation in 8 (6.4%) SSc patients, with a mean value of 37.8 ± 1.2 mm (range 37-40 mm). Aortic root dilation was observed in only one patient in the subgroup 1 (1/62, 1.6%) and in 7 cases of the subgroup 2 (7/63, 11.1%; p = 0.03). Our study found a significant association between aortic root dilation and impairment of capillary density at nailfold videocapillaroscopy in SSc patients. We hypothesize that SSc-related microangiopathy revealed by nailfold videocapillaroscopy could mimic that of aortic vasa vasorum, contributing to deteriorate the aortic wall structure and favoring aortic root dilation and stiffening.
Published: 2021
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41. Pain threshold and intensity in rheumatic patients: correlations with the Hamilton Depression Rating scale.

Author: Bagnato G, De Andres I, Sorbara S, Verduci E, Corallo G, Ferrera A, Morgante S, Roberts WN Jr, and Bagnato G
Subjects: Adult, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Linear Models, Male, Middle Aged, Severity of Illness Index, Sex Factors, Arthritis, Rheumatoid psychology, Pain Threshold, Spondylarthropathies psychology
Abstract: Individuals suffering from chronic pain are frequently affected by depression, which in turn increases the risk of developing chronic pain over time. This study aims to investigate the relationship between depression and pain intensity and threshold in a group of rheumatic patients compared to healthy subjects. One hundred twenty-four individuals of whom 50 were affected by rheumatoid arthritis (RA), 23 by psoriatic arthritis (PsA), 23 by ankylosing spondylitis (AS), and 28 age-matched controls without chronic pain underwent quantitative sensory testing to assess pressure pain threshold with pressure algometry. Pain intensity was evaluated through the visual analogue scale (VAS) and depression through the Hamilton Depression Rating scale (HAMD). A significant inverse correlation between HAMD values and pressure pain thresholds was found in the entire group of patients (p < 0.0001), in controls (p = 0.02), and also in RA (p = 0.002), PsA (p < 0.0002), and AS (p = 0.02) patients when analyzed separately, while no significant correlation was found between HAMD and VAS values or pressure pain thresholds and VAS. We found lower pain thresholds in RA and PsA patients while no difference has been evidenced in AS patients compared to healthy controls. HAMD scores were also significantly higher in rheumatic patients than in controls. The use of pressure algometry in the evaluation of chronic pain in patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis that display comorbid depression could represent an additional and integrative method to improve pain/depression overlap management or research.
Published: 2015
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42. Reassessing morphine effects in cats: III. Responses of intact, caudate nuclei-lesioned and hemispherectomized animals following chronic administration and precipitated withdrawal.

Author: Harris CM, Villablanca JR, Burgess JW, and de Andres I
Subjects: Animals, Arousal drug effects, Cats, Disease Models, Animal, Drug Tolerance, Functional Laterality drug effects, Humans, Male, Morphine adverse effects, Morphine Dependence, Substance Withdrawal Syndrome, Caudate Nucleus drug effects, Cerebral Cortex drug effects, Morphine pharmacology, Stereotyped Behavior drug effects
Abstract: Behavioral response to low doses of morphine (2.0 to 3.0 mg/kg, IP) administered for up to 15 days, and responses to subsequent naloxone challenges, were measured in intact, unilaterally and bilaterally caudate-lesioned (acaudate) cats, and in hemispherectomized cats using a video time-sampling method. For all groups minor tolerance to posture and movement activation patterns was seen, with a reciprocal increase in motor relaxation, which was somewhat more marked for acaudate cats. In contrast to this weak tolerance, all cats showed strong, typical withdrawal manifestations at the beginning of abstinence and a "mini withdrawal" could still be precipitated 15-30 days later when morphine was no longer detectable in the blood. The cats with the unilateral lesions showed whole body turning toward the lesioned side after morphine and away from the lesioned side following naloxone. Only hemispherectomized and acaudate animals showed significant physical deterioration (e.g., weight loss, decreased activity). The comparisons between weak tolerance development versus strong physical dependence and the possible mechanisms involved in shifting the turning biases are discussed. The potential of the cat as a model for studying opiate effects is stressed.
Published: 1984
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43. Independence of sleep-wakefulness cycle in an implanted head 'encephale isole'.

Author: De Andres I, Gutierrez-Rivas E, Nava E, and Reinoso-Suarez F
Abstract: A quantitative study was carried out on the sleep-wakefulness cycle by means of EEG recordings taken simultaneously from a dog's implanted head and its host. During survival (108 h), neurological activities of the implanted head were similar to those of classic 'encéphale isolé' preparations. In spite of a common circulation, the sleep-wakefulness cycles of the implanted head and host animal were independent. Independence was manifested by: (1) differing percentages of respective phases of their cycles; (2) periods of coincident phases in both heads, only occasionally beginning and/or stopping simultaneously; and (3) the implanted 'encéphale isolé' showed a monotonous cycle with numerous periods of short duration throughout night or day. The host presented a nycthemeral rhythm.
Published: 1976
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44. Visually-evoked potentials elicited by a light-emitting diode chronically implanted in the frontal sinus of the freely moving cat.

Author: Siguenza JA, de Andres I, and Reinoso-Suarez F
Subjects: Animals, Cats, Frontal Sinus, Male, Retina physiology, Visual Cortex physiology, Visual Pathways physiology, Evoked Potentials, Visual, Photic Stimulation instrumentation
Abstract: Visually-evoked potentials (VEPs) were obtained with a small yellow light-emitting diode (LED), chronically implanted in the frontal sinus of the cat. The VEPs obtained in scotopic conditions through the LED have a similar morphology to those obtained with a stroboscopic flash. A noticeable delay was observed in LED wave latencies versus flash values. Analysis of wave intervals indicated a long-lasting generation of LED VEPs primary components. Secondary responses have a similar pattern with both modalities of stimulation. Implanted LEDs can be used as a reliable method to obtain VEPs and especially in those behavioural or pathological conditions in which variations exist in the constancy of the ocular media.
Published: 1982
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45. Reassessing morphine effects in cats: II. Protracted effects on sleep-wakefulness and the EEG.

Author: de Andres I, Villablanca JR, and Burgess JW
Subjects: Animals, Cats, Humans, Male, Rats, Sleep Stages drug effects, Stereotyped Behavior drug effects, Electroencephalography, Morphine pharmacology, Sleep drug effects
Abstract: Adult cats were implanted with standard electrodes to record EEG, EOG, and EMG. After 15 days, morphine sulphate or saline placebo was given IP at 0.5, 1.0, 2.0, 3.0 mg/kg, at least 15 days apart. Cats were continuously recorded for 72 hr postinjection. Wakefulness, drowsiness, NREM and REM sleep percentages were scored from polygraphic features and statistically analysed. There was a dose-dependent suppression of NREM and REM sleep for at least 6 hours postmorphine, with a progressive sleep recovery thereafter. During the insomnia period there was an EEG/behavioral dissociation where bursts of high-voltage waves were seen over a background of desynchrony; meanwhile the animal was first aroused although quiet and later showed stereotypic behavior. There was a prolonged NREM sleep rebound which started later at the higher doses. A significant, relatively brief REM sleep rebound was seen only at the lowest dose. The latency for NREM and REM sleep onset was also dose-dependent. Possible brain sites of morphine actions and similarities with effects in other species are discussed.
Published: 1984
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46. Reassessing morphine effects in cats: I. Specific behavioral responses in intact and unilaterally brain-lesioned animals.

Author: Villablanca JR, Harris CM, Burgess JW, and de Andres I
Subjects: Animals, Brain Mapping, Cats, Corpus Striatum physiology, Male, Movement drug effects, Posture drug effects, Substantia Nigra physiology, Behavior, Animal drug effects, Caudate Nucleus drug effects, Cerebral Cortex drug effects, Functional Laterality drug effects, Morphine pharmacology
Abstract: Behavioral responses to single low doses of morphine (0.5-3.0 mg/kg IP) were measured in intact cats and in cats with removal of one cerebral hemisphere or one caudate nucleus. Responses were dose-dependent and formed 3 stages: (1) autonomic stage (0-15 min postdrug): with vocalization, salivation, licking, swallowing, retching and vomiting; (2) quiet stage (15-60 min postdrug): sitting, fixed gaze, mydriasis, and pricked pinnae; (3) head movement stage (from 30-60 min postdrug and decreasing by the 5th hr): fully aroused but mostly sitting; showing discrete, complex head movements of a visual-tracking type with pouncing/avoidance paw movements, and with irregular, dose-dependent bouts of rocking, pivoting, and backing. Sleep, grooming, micturition and defecation were suppressed. In hemispherectomized cats the frequency of head movements was increased only towards the side of the ablation, and there was a strong bias for body turning to that side together with a significant bias to move the ispilateral paw. None of these biases were significant in cats with a unilateral caudate ablation. We conclude that the cat is an excellent model for behavioral morphine studies when dose levels below those inducing "feline mania" are used. CNS sites underlying these responses are discussed.
Published: 1984
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