Search

Your search keyword '"Armando Gabrielli"' showing total 340 results
Start Over Author "Armando Gabrielli"
340 results on '"Armando Gabrielli"'

1. Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis

Author

Anja Wyss, Suzana Jordan, Nicole Graf, Patricia E. Carreira, Jörg Distler, Marco Matucci Cerinic, Elise Siegert, Jörg Henes, Elisabetta Zanatta, Valeria Riccieri, Marie-Elise Truchetet, Fahrettin Oksel, Mengtao Li, Eugene J. Kucharz, Kilian Eyerich, Francesco Del Galdo, Madelon C. Vonk, Anna-Maria Hoffman Vold, Armando Gabrielli, Oliver Distler, and EUSTAR collaborators

Subjects
Scleroderma and related disorders, Skin, Observation studies, Rare diseases, Respiratory, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Objective Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival. Methods Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and ≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis. Results Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations. Conclusion We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials.

Published
2024
Full Text
View/download PDF

2. Association between TNF-α, cortisol levels, and exposure to PM10 and PM2.5: a pilot study

Author

Jacopo Dolcini, Rosaria Landi, Elisa Ponzio, Laura Picchini, Aurora Luciani, Luca Formenti, Silvia Svegliati Baroni, Armando Gabrielli, Marcello Mario D’Errico, and Pamela Barbadoro

Subjects
Salivary testing, Tumor necrosis factor-alpha, Environmental pollution, Epigenetic process, Methylation, Environmental sciences, GE1-350, Environmental law, K3581-3598
Abstract

Abstract Purpose The most harmful atmospheric pollutant for human health is particulate matter (PM). We analyzed the correlation between short-term lag exposure to PM10 and PM2.5, salivary cortisol and TNF-α level, and methylation levels of the TNF-α promoter. Methods A pilot study including 20 subjects. Eight salivary samples for each subject at various times of the day were collected for comparing cortisol levels and TNFα detection. TNFα promoter methylation levels on salivary DNA were analyzed. Regression analyses were performed using generalized linear mixed models between the different outcomes and 4, 3, 2 and 1 day’s lag values of PM10/PM2.5.Generalized additive mixed model (GAMM) was used to evaluate any potential deviation from linearity. Results Area under the curve with respect to the ground (AUCg) showed a statistically positive association with 4-, 3-, 2-, and 1-day lag of exposure to PM10. Area under the curve with respect to the increase (AUCi) showed a statistically negative association with 4-, 3- and 1-day lag of exposure to PM10. TNFα showed statistically significant association with both exposures, PM10 and PM2.5, at 4-, 3-, 2-, and 1-day lag. Conclusions Regarding cortisol levels there is an increase of overall hormone levels but a less dynamism of the system to answer to external stressors. Increase of TNF-α may reflect increased levels of oxidative stress and inflammation due to pollution exposure.

Published
2024
Full Text
View/download PDF

3. Therapeutic management of fibrosis in systemic sclerosis patients – an analysis from the Swiss EUSTAR cohort

Author

Kevin Windirsch, Suzana Jordan, Mike Oliver Becker, Cosimo Bruni, Rucsandra Dobrota, Muriel Elhai, Ion-Alexandru Garaiman, Carmen-Marina Mihai, Michele Iudici, Paul Hasler, Camillo Ribi, Britta Maurer, Armando Gabrielli, Anna-Maria Hoffmann-Vold, and Oliver Distler

Subjects
Medicine
Abstract

OBJECTIVES: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. METHODS: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of 0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. CONCLUSION: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

Published
2024
Full Text
View/download PDF

4. The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis—Interstitial Lung Disease in the European Scleroderma Trial and Research Database

Author

Gemma Lepri, Cosimo Bruni, Lorenzo Tofani, Alberto Moggi-Pignone, Martina Orlandi, Sara Tomassetti, Michael Hughes, Francesco Del Galdo, Rosaria Irace, Oliver Distler, Valeria Riccieri, Yannick Allanore, Ana Maria Gheorghiu, Elise Siegert, Jeska De Vries-Bouwstra, Eric Hachulla, Mohammed Tikly, Nemanja Damjanov, Francois Spertini, Luc Mouthon, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Serena Guiducci, Marco Matucci-Cerinic, Daniel Furst, Silvia Bellando-Randone, and EUSTAR Collaborators

Subjects
computed tomography (CT), interstitial lung disease, scleroderma, pulmonary function test, Medicine (General), R5-920
Abstract

Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Published
2024
Full Text
View/download PDF

5. Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

Author

Pavel I Novikov, Thierry Martin, Eric Hachulla, Vanessa Smith, Maurizio Cutolo, Yannick Allanore, Camillo Ribi, Oliver Distler, Britta Maurer, Paolo Airo, Cosimo Bruni, Veronica Codullo, Luc Mouthon, Marie Vanthuyne, Elisabetta Zanatta, Simona Rednic, Ulf Müller-Ladner, Nemanja Damjanov, Anna-Maria Hoffmann-Vold, Michele Iudici, Suzana Jordan, Jean Sibilia, Mengtao Li, Roger Hesselstrand, Elise Siegert, László Czirják, Armando Gabrielli, Dominique Farge Bancel, Yolanda Braun-Moscovici, Nicolas Hunzelmann, Raffaele Pellerito, Jörg Henes, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Merete Engelhart, Valeria Riccieri, Cord Sunderkötter, Francesca Ingegnoli, Francesco Paolo Cantatore, Susanne Ullman, Maria Rosa Pozzi, Piotr Wiland, Juan Jose Alegre-Sancho, Brigitte Krummel-Lorenz, Ellen De Langhe, Branimir Anic, Carolina de Souza Müller, Simon Stebbings, Alessandra Vacca, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Edoardo Rosato, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Ira Litinsky, Lesley Ann Saketkoo, Eduardo Kerzberg, Tim Schmeiser, Piercarlo Sarzi Puttini, Fabio Cacciapaglia, Marie-Elise Truchetet, Muriel Elhai, Juan José Alegre Sancho, Ivan Castellví, Serena Vettori, Vivien M Hsu, Masataka Kuwana, Sule Yavuz, Radim Becvar, Patricia E Carreira, Eugene J Kucharz, Bernard Coleiro, Paul Hasler, Carlos de la Puente, Svetlana Agachi, Thierry Zenone, Francesco Del Galdo, Doron Rimar, Alessandro Giollo, Lidia P Ananieva, Ina Kötter, Mislav Radic, Dominik Majewski, Kristine Herrmann, Goda Seskute, Lorinda S Chung, Laura Belloli, Ulrike Held, FJ López-Longo, Joerg H W Distler, Maria João Salvador, Simon Kuster, Klaus Steigmiller, Ana-Maria Gheorghiu, Katarzyna Romanowska-Prochnicka, Yuichiro Shirai, Chris Denton, Ruxandra M Ionescu, Stefan Heitmann Vera Ortiz-Santamaria, Walid Ahmed Abdel Atty Mohamed, Paloma Garcíadela Peña Lefebvre, and Vera Bernardino

Subjects
Medicine
Abstract

Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Published
2022
Full Text
View/download PDF

6. Arthroscopic incidence of lateral meniscal root avulsion in patients with anterior cruciate ligament injury

Author

Riccardo Ciatti, Armando Gabrielli, Germando Iannella, and Pier Paolo Mariani

Subjects
Meniscal root, ACL injury, Lateral meniscus, Incidence, Knee, Orthopedic surgery, RD701-811
Abstract

Abstract Background To arthroscopically evaluate the incidence of lateral meniscal root avulsion (LMRA) and associated intra-articular injuries in patients undergoing anterior cruciate ligament (ACL) reconstruction. Materials and Methods From April 2014 to March 2017, 532 consecutive patients were diagnosed as having an ACL injury and underwent arthroscopic ACL reconstruction. The diagnosis of LMRA was made arthroscopically. The effects of gender, activity, grade of laxity, time from injury, and concomitant meniscal lesions were analyzed. Results Among 532 patients, 497 (93.4%) underwent primary ACL reconstruction and 35 (6.5%) underwent revision procedures. 383 were acute or subacute injuries (less than 6 months from injury to surgery) and 149 chronic (more than 6 months). Average age was 30.4 years (DS: ± 11.04); there were 422 (79.3%) males and 110 (20.6%) females. A LMRA associated with the ACL injury was detected in 72 cases (13.5%), with a significant prevalence observed in males ( $${\chi ^2}$$ χ 2 = 4.65; P = 0.031, statistically significant). In the 149 patients with a chronic injury, 27 patients had LMRA (18.1%), while 45 of the 383 patients with an acute or subacute injury had LMRA (11.7%). There was a tendency, albeit not significant ( $${\chi ^2}$$ χ 2 = 3.721; P = 0.054), for the prevalence to increase with time since the initial ACL injury. LMRA was significantly associated ( $${\chi ^2}$$ χ 2 = 7.81; P = 0.006) with a meniscocapsular tear of the posterior horn of the medial meniscus (ramp lesion). No other significant associations, such as with severity of A-P translation (as measured by KT-2000) or activity level, were detected. Conclusion LMRA is a relatively common injury associated with both acute and chronic ACL tears. A relatively high incidence in cases of chronic ACL insufficiency suggests that LMRAs do not heal spontaneously or that they may appear with time, even when absent at the time of the initial injury. Level of evidence Level III, cross-sectional study.

Published
2021
Full Text
View/download PDF

7. The burden of systemic sclerosis in Switzerland – the Swiss systemic sclerosis EUSTAR cohort

Author

Jasmin Hernández, Suzana Jordan, Rucsandra Dobrota, Michele Iudici, Paul Hasler, Camillo Ribi, Peter Villiger, Panayiotis Vlachoyiannopoulos, Alessandra Vacca, Ludmila Garzanova, Alessandro Giollo, Edoardo Rosato, Ina Kötter, Patricia E. Carreira, Andrea Doria, Jörg Henes, Ulf Müller-Ladner, Vanessa Smith, Jörg Distler, Armando Gabrielli, Anna-Maria Hoffman-Vold, Ulrich Walker, Oliver Distler, and the EUSTAR collaborators

Subjects
systemic sclerosis, Switzerland, Europe, Medicine
Abstract

OBJECTIVES Characteristics of Swiss patients with systemic sclerosis have not been described so far. The aim of the current study was to identify unmet needs in comparison with other European countries that could inform specific interventions to improve the care of systemic sclerosis patients. METHODS We analysed Swiss and other European systemic sclerosis patients registered in European Scleroderma Trials And Research (EUSTAR) and the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) cohort. Demographics, clinical profiles, organ involvement and survival of established, early/mild and very early / very mild systemic sclerosis patients were described and compared between the cohorts. RESULTS We included 679 Swiss and 8793 European systemic sclerosis patients in the analysis. Over 95% of patients in both cohorts were Caucasian, disease subsets were similar, and no age difference was found. The Swiss cohort had more male patients (25% vs 16% European, p = 0.005) and higher prevalence of early/mild and very early / very mild patients (26.1 vs 8.5% European and 14.9% vs 6.7% European, respectively, both p

Published
2021
Full Text
View/download PDF

8. GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Author

Elena López-Isac, Marialbert Acosta-Herrera, Martin Kerick, Shervin Assassi, Ansuman T. Satpathy, Jeffrey Granja, Maxwell R. Mumbach, Lorenzo Beretta, Carmen P. Simeón, Patricia Carreira, Norberto Ortego-Centeno, Ivan Castellvi, Lara Bossini-Castillo, F. David Carmona, Gisela Orozco, Nicolas Hunzelmann, Jörg H. W. Distler, Andre Franke, Claudio Lunardi, Gianluca Moroncini, Armando Gabrielli, Jeska de Vries-Bouwstra, Cisca Wijmenga, Bobby P. C. Koeleman, Annika Nordin, Leonid Padyukov, Anna-Maria Hoffmann-Vold, Benedicte Lie, European Scleroderma Group, Susanna Proudman, Wendy Stevens, Mandana Nikpour, Australian Scleroderma Interest Group (ASIG), Timothy Vyse, Ariane L. Herrick, Jane Worthington, Christopher P. Denton, Yannick Allanore, Matthew A. Brown, Timothy R. D. J. Radstake, Carmen Fonseca, Howard Y. Chang, Maureen D. Mayes, and Javier Martin

Subjects
Science
Abstract

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

Published
2019
Full Text
View/download PDF

10. Biomarkers in Inflammatory Bowel Disease-Associated Spondyloarthritis: State of the Art and Unmet Needs

Author

Devis Benfaremo, Michele Maria Luchetti, and Armando Gabrielli

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Inflammatory bowel disease-associated spondyloarthritis is a systemic disease characterized by the chronic inflammation of both the gastrointestinal tract and the musculoskeletal system. Since inflammatory bowel disease-associated spondyloarthritis has been associated with a significant diagnostic delay, which may lead to poor quality of life and progression of joint damage, efforts to discover new reliable and noninvasive diagnostic biomarkers have been made. We reviewed the state of the art of biomarker research in inflammatory bowel disease-associated spondyloarthritis, showing that to date it has been largely unsatisfactory. Only a few of the biomarkers that have been investigated are likely to enter the clinical practice upon further validation in independent cohorts. The research of new and innovative biomarkers for inflammatory bowel disease-associated spondyloarthritis is warranted.

Published
2019
Full Text
View/download PDF

11. Is There a Future for Anti-CD38 Antibody Therapy in Systemic Autoimmune Diseases?

Author

Devis Benfaremo and Armando Gabrielli

Subjects
anti-cd38, autoimmune diseases, plasmablast, plasma cells, systemic sclerosis, ssc, systemic lupus erythematosus, sle, Cytology, QH573-671
Abstract

CD38 is a type II glycoprotein highly expressed on plasmablasts, short-lived and long-lived plasma cells, but weakly expressed on other lymphoid cells, myeloid cells and non-hematopoietic cells. This expression pattern makes CD38 an interesting target for a targeted therapy aiming to deplete antibody-producing plasma cells. We present data suggesting that anti-CD38 therapy may be effective for the prevention at the preclinical stage and for the treatment of established autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Given the high unmet need for efficacious disease-modifying treatment in these diseases, studies are warranted to determine if anti-CD38 antibody-based therapies may delay or prevent the disease progression of systemic autoimmune diseases.

Published
2019
Full Text
View/download PDF

12. Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice.

Author

Gianluca Moroncini, Chiara Paolini, Fiorenza Orlando, Chiara Capelli, Antonella Grieco, Cecilia Tonnini, Silvia Agarbati, Eleonora Mondini, Stefania Saccomanno, Gaia Goteri, Silvia Svegliati Baroni, Mauro Provinciali, Martino Introna, Nicoletta Del Papa, and Armando Gabrielli

Subjects
Medicine, Science
Abstract

Lung fibrosis is a severe condition resulting from several interstial lung diseases (ILD) with different etiologies. Current therapy of ILD, especially those associated with connective tissue diseases, is rather limited and new anti-fibrotic strategies are needed. In this study, we investigated the anti-fibrotic activity in vivo of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC). Adult immunocompetent C57BL/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 × 105) twice, 24 hours and 7 days after endotracheal injection of bleomycin. Upon sacrifice at days 8, 14, 21, collagen content, inflammatory cytokine profile, and hUC-MSC presence in explanted lung tissue were analyzed. Systemic administration of a double dose of hUC-MSC significantly reduced bleomycin-induced lung injury (inflammation and fibrosis) in mice through a selective inhibition of the IL6-IL10-TGFβ axis involving lung M2 macrophages. Only few hUC-MSC were detected from explanted lungs, suggesting a "hit and run" mechanism of action of this cellular therapy. Our data indicate that hUC-MSC possess strong in vivo anti-fibrotic activity in a mouse model resembling an immunocompetent human subject affected by inflammatory ILD, providing proof of concept for ad-hoc clinical trials.

Published
2018
Full Text
View/download PDF

13. Asymptomatic endoalveolar hemorrhage in a young male

Author

Alain Kafyeke, Giovanni Pomponio, Andrea Balloni, Simona Gambini, Francesca Barbisan, and Armando Gabrielli

Subjects
Wegener’s granulomatosis, hemorrhage, bronchoalveolar lavage., Medicine
Abstract

We describe the case of a young male affected by granulomatosis with polyangiitis presenting with non-specific complaints and complicated by the occurrence of a diffuse endoalveolar hemorrhage characterized by atypical clinical and radiological features. The importance of a rapid and aggressive diagnostic and therapeutic approach has to be strongly underlined. Available data regarding prevalence, clinical and radiological characteristics and treatment of this uncommon manifestation have also been hereby reviewed.

Published
2016
Full Text
View/download PDF

14. Isolated Aortitis Presenting with an Annoying Persistent Cough: A Case Report

Author

Michele Maria Luchetti, William Capeci, Matteo Rossini, Devis Benfaremo, and Armando Gabrielli

Subjects
Aortitis, chronic cough, rare diseases, Medicine
Abstract

Objectives: To report a case of idiopathic aortitis presenting with chronic cough. Materials and Methods: the Authors describe the case of a 72-year-old man with dry cough, worsening fatigue, weight loss and elevated systemic inflammatory markers. Results: A PET-CT scan showed diffuse thickening of the thoracic aorta and confirmed the diagnosis of aortitis. Systemic corticosteroid therapy was initiated and complete remission was achieved in six months. Conclusion: Persistent dry cough of unknown origin, especially when associated with systemic inflammation, demands a thorough differential diagnosis and should not be underrated.

Published
2016
Full Text
View/download PDF

15. Reply to J. Magalon et al.

Author

Nicoletta Del Papa, Gabriele Di Luca, Domenico Sambataro, Eleonora Zaccara, Wanda Maglione, Armando Gabrielli, Paolo Fraticelli, Gianluca Moroncini, Lorenzo Beretta, Alessandro Santaniello, Gianluca Sambataro, Roberto Ferraresi, and Claudio Vitali

Subjects
Medicine
Published
2015
Full Text
View/download PDF

16. Regional Implantation of Autologous Adipose Tissue-Derived Cells Induces a Prompt Healing of Long-Lasting Indolent Digital Ulcers in Patients with Systemic Sclerosis

Author

Nicoletta Del Papa M.D., Gabriele Di Luca, Domenico Sambataro, Eleonora Zaccara, Wanda Maglione, Armando Gabrielli, Paolo Fraticelli, Gianluca Moroncini, Lorenzo Beretta, Alessandro Santaniello, Gianluca Sambataro, Roberto Ferraresi, and Claudio Vitali

Subjects
Medicine
Abstract

Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5-1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2-7 weeks). A significant reduction of pain intensity was observed after a few weeks ( p < 0.001), while the number of capillaries was significantly increased at 3- and 6-month NVC assessment ( p < 0.0001 in both cases). Finally, a significant after-treatment reduction of digit artery resistivity was also recorded ( p < 0.0001). Even with the limitations related to the small number of patients included and to the open-label design of the study, the observed strongly favorable outcome suggests that local grafting with ATDCs could represent a promising option for the treatment of SSc-related DUs unresponsive to more consolidated therapies.

Published
2015
Full Text
View/download PDF

17. Plasma free hemoglobin and microcirculatory response to fresh or old blood transfusions in sepsis.

Author

Elisa Damiani, Erica Adrario, Michele Maria Luchetti, Claudia Scorcella, Andrea Carsetti, Nicoletta Mininno, Silvia Pierantozzi, Tiziana Principi, Daniele Strovegli, Rosella Bencivenga, Armando Gabrielli, Rocco Romano, Paolo Pelaia, Can Ince, and Abele Donati

Subjects
Medicine, Science
Abstract

Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098-0.219] mg/mL to 0.238 [0.163-0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.ClinicalTrials.gov NCT01584999.

Published
2015
Full Text
View/download PDF

18. Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody

Author

Gianluca Moroncini, Michela Mangieri, Michela Morbin, Giulia Mazzoleni, Bernardino Ghetti, Armando Gabrielli, Robert Anthony Williamson, Giorgio Giaccone, and Fabrizio Tagliavini

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Prion diseases are characterized by the accumulation in the brain of abnormal conformers (PrPSc) of the cellular prion protein (PrPC).PrPSc immunohistochemistry, currently based on antibodies non-distinguishing between PrPC and PrPSc, requires pre-treatments of histological sections to eliminate PrPC and to denature PrPSc. We employed the PrPSc-specific antibody 89–112 PrP motif-grafted IgG on mildly fixed, untreated brain sections from several cases of human prion diseases. The results confirmed specific binding of IgG 89–112 to a structural determinant found exclusively on native disease-associated PrP conformations and lost following tissue denaturation or cross-linking fixation. Importantly, IgG 89–112 demonstrated no reactivity with normal brain tissue or with amyloid deposits in Alzheimer disease brain sections. Thus, immunohistochemical detection of native PrPSc deposits was obtained by means of a PrPSc-specific antibody. Such unique reagent may have many applications in the study of prion biology and in the diagnosis and prevention of prion diseases.

Published
2006
Full Text
View/download PDF

19. High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

Author

Paola Adele Lonati, Nicolò Costantino Brembilla, Elisa Montanari, Lionel Fontao, Armando Gabrielli, Serena Vettori, Gabriele Valentini, Emmanuel Laffitte, Gurkan Kaya, Pier-Luigi Meroni, and Carlo Chizzolini

Subjects
Medicine, Science
Abstract

BackgroundHigh interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis.MethodsBiopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA.ResultsPositive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p = 0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration.ConclusionsThe frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low) and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL-17E cytokine combination may thus play a role in the development of fibrosis.

Published
2014
Full Text
View/download PDF

20. Reactive oxygen species are required for maintenance and differentiation of primary lung fibroblasts in idiopathic pulmonary fibrosis.

Author

Marialuisa Bocchino, Savina Agnese, Evelina Fagone, Silvia Svegliati, Domenico Grieco, Carlo Vancheri, Armando Gabrielli, Alessandro Sanduzzi, and Enrico V Avvedimento

Subjects
Medicine, Science
Abstract

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal illness whose pathogenesis remains poorly understood. Recent evidence suggests oxidative stress as a key player in the establishment/progression of lung fibrosis in animal models and possibly in human IPF. The aim of the present study was to characterize the cellular phenotype of fibroblasts derived from IPF patients and identify underlying molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the baseline differentiation features and growth ability of primary lung fibroblasts derived from 7 histology proven IPF patients and 4 control subjects at different culture passages. Then, we focused on the redox state and related molecular pathways of IPF fibroblasts and investigated the impact of oxidative stress in the establishment of the IPF phenotype. IPF fibroblasts were differentiated into alpha-smooth muscle actin (SMA)-positive myofibroblasts, displayed a pro-fibrotic phenotype as expressing type-I collagen, and proliferated lower than controls cells. The IPF phenotype was inducible upon oxidative stress in control cells and was sensitive to ROS scavenging. IPF fibroblasts also contained large excess of reactive oxygen species (ROS) due to the activation of an NADPH oxidase-like system, displayed higher levels of tyrosine phosphorylated proteins and were more resistant to oxidative-stress induced cell death. Interestingly, the IPF traits disappeared with time in culture, indicating a transient effect of the initial trigger. CONCLUSIONS/SIGNIFICANCE: Robust expression of α-SMA and type-I collagen, high and uniformly-distributed ROS levels, resistance to oxidative-stress induced cell death and constitutive activation of tyrosine kinase(s) signalling are distinctive features of the IPF phenotype. We suggest that this phenotype can be used as a model to identify the initial trigger of IPF.

Published
2010
Full Text
View/download PDF

21. Inflammation and DNA damage: cause, effect or both

Author

Antonio Pezone, Fabiola Olivieri, Maria Vittoria Napoli, Antonio Procopio, Enrico Vittorio Avvedimento, Armando Gabrielli, Pezone, Antonio, Olivieri, Fabiola, Vittoria Napoli, Maria, Procopio, Antonio, Vittorio Avvedimento, Enrico, and Gabrielli, Armando

Subjects
Rheumatology
Abstract

Inflammation is a biological response involving immune cells, blood vessels and mediators induced by endogenous and exogenous stimuli, such as pathogens, damaged cells or chemicals. Unresolved (chronic) inflammation is characterized by the secretion of cytokines that maintain inflammation and redox stress. Mitochondrial or nuclear redox imbalance induces DNA damage, which triggers the DNA damage response (DDR) that is orchestrated by ATM and ATR kinases, which modify gene expression and metabolism and, eventually, establish the senescent phenotype. DDR-mediated senescence is induced by the signalling proteins p53, p16 and p21, which arrest the cell cycle in G1 or G2 and promote cytokine secretion, producing the senescence-associated secretory phenotype. Senescence and inflammation phenotypes are intimately associated, but highly heterogeneous because they vary according to the cell type that is involved. The vicious cycle of inflammation, DNA damage and DDR-mediated senescence, along with the constitutive activation of the immune system, is the core of an evolutionarily conserved circuitry, which arrests the cell cycle to reduce the accumulation of mutations generated by DNA replication during redox stress caused by infection or inflammation. Evidence suggests that specific organ dysfunctions in apparently unrelated diseases of autoimmune, rheumatic, degenerative and vascular origins are caused by inflammation resulting from DNA damage-induced senescence.

Published
2023

22. Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from the EUSTAR cohort

Author

Elisabetta Zanatta 1, Dörte Huscher 2, Augusta Ortolan 1, Jérôme Avouac 3, Paolo Airò 4, Alexandra Balbir-Gurman 5, Elise Siegert 6, Marco Matucci Cerinic 7, Franco Cozzi 8, Gabriela Riemekasten 9, Anna-Maria Hoffmann-Vold 10, Oliver Distler 11, Armando Gabrielli 12, Stefan Heitmann 13, Nicolas Hunzelmann 14, Carlomaurizio Montecucco 15, Jadranka Morovic-Vergles 16, Camillo Ribi 17, Andrea Doria 1, Yannick Allanore 3, EUSTAR collaborators, Giovanna Cuomo, Gianluca Moroncini, Jiri Stork, Fiorenzo Iannone, Ulrich Walker, Eugenia Bertoldo, Dorota Krasowska, Maria João Salvador, Mohammed Tikly, Eric Hachulla, Valeria Riccieri, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Branimir Anic, Maria Üprus, Brigitte Granel, Alessandra Vacca, Cristina-Mihaela Tanaseanu, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Lesley Ann Saketkoo, Eduardo Kerzberg, Massimiliano Limonta, Doron Rimar, Petros Sfikakis, Maurizio Cutolo, Patricia E Carreira, Rosario Foti, Srdan Novak, Michele Iudici, Mislav Radic, Raffaele Pellerito, Carlo Francesco Selmi, Lidia P Ananieva, Gabriela Szücs, Carlos de la Puente, Ruxandra Maria Ionescu, Jörg Distler, Maria Rosa Pozzi, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Sule Yavuz, Carolina de Souza Müller, Svetlana Agachi, Douglas Veale, Esthela Loyo, Mengtao Li, Edoardo Rosato, Britta Maurer, Ivan Castellví, François Spertini, Kamal Solanki, Nicoletta Del Papa, Gerard Espinosa, László Czirják, Bernard Coleiro, Dominique Farge Bancel, Christopher Denton, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Michaela Kohm, Bojana Stamenkovic, 1, Elisabetta Zanatta, 2, Dörte Huscher, 1, Augusta Ortolan, 3, Jérôme Avouac, 4, Paolo Airò, 5, Alexandra Balbir-Gurman, 6, Elise Siegert, 7, Marco Matucci Cerinic, 8, Franco Cozzi, 9, Gabriela Riemekasten, Hoffmann-Vold 10, Anna-Maria, Distler 11, Oliver, Gabrielli 12, Armando, Heitmann 13, Stefan, Hunzelmann 14, Nicola, Montecucco 15, Carlomaurizio, Morovic-Vergles 16, Jadranka, Ribi 17, Camillo, 1, Andrea Doria, 3, Yannick Allanore, Collaborators, Eustar, Cuomo, Giovanna, Moroncini, Gianluca, Stork, Jiri, Iannone, Fiorenzo, Walker, Ulrich, Bertoldo, Eugenia, Krasowska, Dorota, João Salvador, Maria, Tikly, Mohammed, Hachulla, Eric, Riccieri, Valeria, Sha, Ami, Maria Gheorghiu, Ana, Sunderkötter, Cord, Ingegnoli, Francesca, Mouthon, Luc, Smith, Vanessa, Paolo Cantatore, Francesco, Eyerich, Kilian, Wiland, Piotr, Vanthuyne, Marie, Anic, Branimir, Üprus, Maria, Granel, Brigitte, Vacca, Alessandra, Tanaseanu, Cristina-Mihaela, García de la Peña Lefebvre, Paloma, Sibilia, Jean, Litinsky, Ira, Ann Saketkoo, Lesley, Kerzberg, Eduardo, Limonta, Massimiliano, Rimar, Doron, Sfikakis, Petro, Cutolo, Maurizio, E Carreira, Patricia, Foti, Rosario, Novak, Srdan, Iudici, Michele, Radic, Mislav, Pellerito, Raffaele, Francesco Selmi, Carlo, P Ananieva, Lidia, Szücs, Gabriela, de la Puente, Carlo, Maria Ionescu, Ruxandra, Distler, Jörg, Rosa Pozzi, Maria, Jose Alegre-Sancho, Juan, Herrmann, Kristine, De Langhe, Ellen, Yavuz, Sule, de Souza Müller, Carolina, Agachi, Svetlana, Veale, Dougla, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Maurer, Britta, Castellví, Ivan, Spertini, Françoi, Solanki, Kamal, Del Papa, Nicoletta, Espinosa, Gerard, Czirják, László, Coleiro, Bernard, Farge Bancel, Dominique, Denton, Christopher, Damjanov, Nemanja, Henes, Jörg, Ortiz Santamaria, Vera, Kohm, Michaela, and Stamenkovic, Bojana

Subjects
interstitial lung disease, Scleroderma, Systemic, Hypertension, Pulmonary, disease subset, anti-topoisomerase I, Scleroderma, Systemic sclerosis, cutaneous form, outcome, Phenotype, Rheumatology, Scleroderma, Limited, Antibodies, Antinuclear, Scleroderma, Diffuse, Humans, Pharmacology (medical), Lung Diseases, Interstitial
Abstract

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Published
2022

23. Early administration of tofacitinib in <scp>COVID</scp> ‐19 pneumonitis: An open randomised controlled trial

Author

Alessia Ferrarini, Angelo Vacca, Antonio Giovanni Solimando, Marcello Tavio, Rossella Acquaviva, Marco Rocchi, Cinzia Nitti, Aldo Salvi, Vincenzo Menditto, Michele Maria Luchetti Gentiloni, Alessandro Russo, Marco Moretti, Marianna Pavani, Andrea Giacometti, Martina Bonifazi, Lina Zuccatosta, Laura Romani, Vito Racanelli, Gianluca Moroncini, Armando Gabrielli, and Giovanni Pomponio

Subjects
Clinical Biochemistry, General Medicine, Biochemistry
Abstract

Controversies on sub-populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID-19.We designed a multicentre open-label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID-19 pneumonitis.Patients admitted to three Italian hospitals affected by COVID-19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission.A total of 116 patients were randomised; 49 in the experimental arm completed the 14-day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SOHigh-dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.

Published
2022

24. Arthroscopic incidence of lateral meniscal root avulsion in patients with anterior cruciate ligament injury

Author

Pier Paolo Mariani, Armando Gabrielli, Riccardo Ciatti, and Germando Iannella

Subjects
medicine.medical_specialty, Sports medicine, Anterior cruciate ligament, Menisci, Tibial, Avulsion, 03 medical and health sciences, Arthroscopy, 0302 clinical medicine, medicine, Humans, Orthopedics and Sports Medicine, Knee, Anterior Cruciate Ligament, Lateral meniscus, Meniscal root, Rupture, Orthopedic surgery, 030222 orthopedics, ACL injury, Anterior Cruciate Ligament Reconstruction, business.industry, Anterior Cruciate Ligament Injuries, Incidence, 030229 sport sciences, medicine.disease, Surgery, medicine.anatomical_structure, Cross-Sectional Studies, Italy, Tears, Original Article, business, Medial meniscus, RD701-811
Abstract

Background To arthroscopically evaluate the incidence of lateral meniscal root avulsion (LMRA) and associated intra-articular injuries in patients undergoing anterior cruciate ligament (ACL) reconstruction. Materials and Methods From April 2014 to March 2017, 532 consecutive patients were diagnosed as having an ACL injury and underwent arthroscopic ACL reconstruction. The diagnosis of LMRA was made arthroscopically. The effects of gender, activity, grade of laxity, time from injury, and concomitant meniscal lesions were analyzed. Results Among 532 patients, 497 (93.4%) underwent primary ACL reconstruction and 35 (6.5%) underwent revision procedures. 383 were acute or subacute injuries (less than 6 months from injury to surgery) and 149 chronic (more than 6 months). Average age was 30.4 years (DS: ± 11.04); there were 422 (79.3%) males and 110 (20.6%) females. A LMRA associated with the ACL injury was detected in 72 cases (13.5%), with a significant prevalence observed in males ($${\chi ^2}$$ χ 2 = 4.65; P = 0.031, statistically significant). In the 149 patients with a chronic injury, 27 patients had LMRA (18.1%), while 45 of the 383 patients with an acute or subacute injury had LMRA (11.7%). There was a tendency, albeit not significant ($${\chi ^2}$$ χ 2 = 3.721; P = 0.054), for the prevalence to increase with time since the initial ACL injury. LMRA was significantly associated ($${\chi ^2}$$ χ 2 = 7.81; P = 0.006) with a meniscocapsular tear of the posterior horn of the medial meniscus (ramp lesion). No other significant associations, such as with severity of A-P translation (as measured by KT-2000) or activity level, were detected. Conclusion LMRA is a relatively common injury associated with both acute and chronic ACL tears. A relatively high incidence in cases of chronic ACL insufficiency suggests that LMRAs do not heal spontaneously or that they may appear with time, even when absent at the time of the initial injury. Level of evidence Level III, cross-sectional study.

Published
2021

25. Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort

Author

Michael, Hughes, Calvin, Heal, Jörg, Henes, Alexandra, Balbir-Gurman, Jörg H W, Distler, Paolo, Airò, Ulf, Müller-Ladner, Nicolas, Hunzelmann, Eduardo, Kerzberg, Lidia, Rudnicka, Marie-Elise, Truchetet, Simon, Stebbings, Yoshiya, Tanaka, Anna Maria, Hoffman-Vold, Armando, Gabrielli, Oliver, Distler, Marco, Matucci-Cerinic, and Ulrich, Walker

Subjects
Adult, Male, medicine.medical_specialty, Telangiectases, Disease, Logistic regression, Cicatrix, Rheumatology, Calcinosis, death, Internal medicine, digital pitting scars, Skin Ulcer, Humans, Medicine, scleroderma, Pharmacology (medical), vasculopathy, Aged, Gangrene, Scleroderma, Systemic, business.industry, Interstitial lung disease, Middle Aged, medicine.disease, Pulmonary hypertension, digital ischaemia, Cohort, Disease Progression, Female, business, SSc
Abstract

Objective Digital pitting scars (DPS) are frequent, but little studied in SSc to date. Methods An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. Results A total of 9671 patients were included with reported DPS at any time point (n = 4924) or ‘never’ DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud’s duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51–24.87), active digital ischaemia: 6.30 (5.34–7.42) and death: 1.86 (1.48–2.36). Conclusion DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

Published
2021

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

Author

Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F

Subjects
Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Published
2021

27. Diagnosis and management of leukocytoclastic vasculitis

Author

Paolo Fraticelli, Armando Gabrielli, and Devis Benfaremo

Subjects
Pathology, medicine.medical_specialty, Diagnosis, Differential, IgA vasculitis, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Internal Medicine, medicine, Humans, Fibrinoid necrosis, Cryoglobulinemic vasculitis, Palpable purpura, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, Small vessel vasculitis, Hypocomplementemic urticarial vasculitis, Leukocytoclastic vasculitis, Prognosis, medicine.disease, Im - Review, Purpura, Emergency Medicine, Vasculitis, Leukocytoclastic, Cutaneous, medicine.symptom, business, Vasculitis, 030217 neurology & neurosurgery, Systemic vasculitis
Abstract

Leukocytoclastic vasculitis (LCV) is a histopathologic description of a common form of small vessel vasculitis (SVV), that can be found in various types of vasculitis affecting the skin and internal organs. The leading clinical presentation of LCV is palpable purpura and the diagnosis relies on histopathological examination, in which the inflammatory infiltrate is composed of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments (“leukocytoclasia”). Several medications can cause LCV, as well as infections, or malignancy. Among systemic diseases, the most frequently associated with LCV are ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic vasculitis, IgA vasculitis (formerly known as Henoch–Schonlein purpura) and hypocomplementemic urticarial vasculitis (HUV). When LCV is suspected, an extensive workout is usually necessary to determine whether the process is skin-limited, or expression of a systemic vasculitis or disease. A comprehensive history and detailed physical examination must be performed; platelet count, renal function and urinalysis, serological tests for hepatitis B and C viruses, autoantibodies (anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies), complement fractions and IgA staining in biopsy specimens are part of the usual workout of LCV. The treatment is mainly focused on symptom management, based on rest (avoiding standing or walking), low dose corticosteroids, colchicine or different unproven therapies, if skin-limited. When a medication is the cause, the prognosis is favorable and the discontinuation of the culprit drug is usually resolutive. Conversely, when a systemic vasculitis is the cause of LCV, higher doses of corticosteroids or immunosuppressive agents are required, according to the severity of organ involvement and the underlying associated disease.

Published
2021

28. Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study—Joint and Skin (BeRLiSS-JS)

Author

Margherita Zen, Mariele Gatto, Roberto Depascale, Francesca Regola, Micaela Fredi, Laura Andreoli, Franco Franceschini, Maria Letizia Urban, Giacomo Emmi, Fulvia Ceccarelli, Fabrizio Conti, Alessandra Bortoluzzi, Marcello Govoni, Chiara Tani, Marta Mosca, Tania Ubiali, Maria Gerosa, Enrica P. Bozzolo, Valentina Canti, Paolo Cardinaletti, Armando Gabrielli, Giacomo Tanti, Elisa Gremese, Ginevra De Marchi, Salvatore De Vita, Serena Fasano, Francesco Ciccia, Giulia Pazzola, Carlo Salvarani, Simone Negrini, Andrea Di Matteo, Rossella De Angelis, Giovanni Orsolini, Maurizio Rossini, Paola Faggioli, Antonella Laria, Matteo Piga, Alberto Cauli, Salvatore Scarpato, Francesca Wanda Rossi, Amato De Paulis, Enrico Brunetta, Angela Ceribelli, Carlo Selmi, Marcella Prete, Vito Racanelli, Angelo Vacca, Elena Bartoloni, Roberto Gerli, Elisabetta Zanatta, Maddalena Larosa, Francesca Saccon, Andrea Doria, Luca Iaccarino, Zen, Margherita, Gatto, Mariele, Depascale, Roberto, Regola, Francesca, Fredi, Micaela, Andreoli, Laura, Franceschini, Franco, Letizia Urban, Maria, Emmi, Giacomo, Ceccarelli, Fulvia, Conti, Fabrizio, Bortoluzzi, Alessandra, Govoni, Marcello, Tani, Chiara, Mosca, Marta, Ubiali, Tania, Gerosa, Maria, Bozzolo, Enrica P., Canti, Valentina, Cardinaletti, Paolo, Gabrielli, Armando, Tanti, Giacomo, Gremese, Elisa, De Marchi, Ginevra, De Vita, Salvatore, Fasano, Serena, Ciccia, Francesco, Pazzola, Giulia, Salvarani, Carlo, Negrini, Simone, Di Matteo, Andrea, DE ANGELIS, Rossella, Orsolini, Giovanni, Rossini, Maurizio, Faggioli, Paola, Laria, Antonella, Piga, Matteo, Cauli, Alberto, Scarpato, Salvatore, Wanda Rossi, Francesca, De Paulis, Amato, Brunetta, Enrico, Ceribelli, Angela, Selmi, Carlo, Prete, Marcella, Racanelli, Vito, Vacca, Angelo, Bartoloni, Elena, Gerli, Roberto, Zanatta, Elisabetta, Larosa, Maddalena, Saccon, Francesca, Doria, Andrea, and Iaccarino, Luca

Subjects
disease activity score (DAS)-28, low disease activity, remission, systemic lupus erythematosus, belimumab, Cutaneous LE Area and Severity Index (CLASI), Medicine (miscellaneous)
Abstract

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (

Published
2023

30. Rituximab for eosinophilic granulomatosis with polyangiitis: a systematic review of observational studies

Author

Alessia Angeletti, Diletta Olivari, Marco B. L. Rocchi, Armando Gabrielli, Giovanni Pomponio, Giulia Rossetti, and Vincenzo G Menditto

Subjects
medicine.medical_specialty, MEDLINE, Cochrane Library, rituximab, systematic review, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective cohort study, observational studies, ANCA-associated vasculitis, eosinophilic granulomatosis with polyangiitis, business.industry, Remission Induction, Granulomatosis with Polyangiitis, Retrospective cohort study, medicine.disease, Clinical trial, Observational Studies as Topic, Treatment Outcome, Observational study, Rituximab, business, Granulomatosis with polyangiitis, Immunosuppressive Agents, medicine.drug
Abstract

Objective To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. Methods A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents. Results Forty-five papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup. Conclusion Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.

Published
2021

31. Novel Therapeutic Approaches and Treatment Targets for Psoriatic Arthritis

Author

Devis Benfaremo, Valentino Paci, Michele Maria Luchetti, and Armando Gabrielli

Subjects
0106 biological sciences, Inflammatory arthritis, MEDLINE, Pharmaceutical Science, Disease, Bioinformatics, 01 natural sciences, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Treatment targets, 010608 biotechnology, Psoriasis, medicine, Humans, Molecular Targeted Therapy, Inflammation, Interleukin-12 Subunit p40, Tumor Necrosis Factor-alpha, business.industry, Arthritis, Psoriatic, Interleukin-17, Antibodies, Monoclonal, medicine.disease, Clinical trial, Antirheumatic Agents, 030220 oncology & carcinogenesis, Interleukin-23 Subunit p19, business, Janus kinase, Biotechnology
Abstract

Background: Psoriatic Arthritis (PsA) is the most common extracutaneous manifestation of psoriasis. This chronic inflammatory arthritis is burdened with significant morbidity, leading to irreversible joint damage and disability. In recent years, a deeper understating of its pathogenesis has led to the development of several new drugs targeting different pathways. Objectives: This review aims to highlight the clinical efficacy and safety of the novel agents that have become recently available for the treatment of PsA, as well as new promising therapeutic targets that are being evaluated in clinical trials. Methods: For the purpose of this narrative review, we searched in the MEDLINE and ClinicalTrials. gov databases. Results: After the introduction of the first biological drugs targeting Tumor Necrosis Factor (TNF), several other drugs with different targets have been developed, including anti-Interleukin (IL) 12/23p40, anti-IL17, and, more recently, anti-IL23p19 agents. Conclusions: Data supporting the efficacy of different agents in the major domains of PsA, as well as their safety issues, are summarized here. Finally, the current pipeline, including several novel nonbiological small molecules, such as Janus kinase (JAK) inhibitors, that are currently being evaluated in clinical trials are also presented. Discussion: The availability of newer therapeutic agents has substantially changed the treatment strategy for PsA. In the future, a personalized treatment approach will probably achieve better control of disease manifestations.

Published
2020

32. Putative functional pathogenic autoantibodies in systemic sclerosis

Author

L. Manfredi, Devis Benfaremo, Gianluca Moroncini, Armando Gabrielli, and Silvia Baroni

Subjects
lcsh:Immunologic diseases. Allergy, 030203 arthritis & rheumatology, Cellular immunity, Systemic disease, Invited Review, integumentary system, business.industry, Autoantibody, Acquired immune system, medicine.disease, Scleroderma, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Fibrosis, Immunology, Medicine, 030212 general & internal medicine, lcsh:RC581-607, skin and connective tissue diseases, business
Abstract

Systemic sclerosis (scleroderma, SSc) is a systemic disease characterized by vascular lesions, fibrosis, and circulating autoantibodies. A complex interplay between innate and adaptive immunity, and with regard to the latter, between humoral and cellular immunity, is believed to be involved in SSc pathogenesis. Lately, close attention has been paid to the role of B cells which, once activated, release profibrotic cytokines, promote profibrotic Th2 differentiation, and produce autoantibodies. Several novel interesting autoantibodies, targeting antigens within the extracellular matrix or on the cell surface, rather than the nuclear antigens of canonical SSc-autoantibodies, have been recently described in patients with SSc. As they show stimulatory or inhibitory activity or react with structures involved in the pathogenesis of SSc lesions, they can be considered as potentially pathogenic. In this paper, we will review those which have been better characterized.

Published
2020

33. Computed tomography assessment of evolution of interstitial lung disease in systemic sclerosis: Comparison of two scoring systems

Author

Armando Gabrielli, Colomba Fischetti, Fausto Salaffi, Marina Carotti, Marco Di Carlo, Paolo Fraticelli, Marika Tardella, and Andrea Giovagnoni

Subjects
medicine.medical_specialty, High-resolution computed tomography, Response to therapy, Computed tomography, 030204 cardiovascular system & hematology, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Humans, In patient, 030212 general & internal medicine, Lung, Retrospective Studies, Scleroderma, Systemic, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Interstitial lung disease, Retrospective cohort study, Gold standard (test), medicine.disease, Radiology, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business
Abstract

Background The aim of this study was to evaluate and compare the internal and external responsiveness of a computed-aided method (CaM) with a conventional visual reader-based score (CoVR) to measure interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) on high resolution computed tomography (HRCT). Methods Forty-five patients were evaluated in this retrospective cohort. HRCTs were collected at baseline and after 1 year. HRCT abnormalities were evaluated according to a CoVR (Warrick's method) and a quantitative CaM. Internal 1-year responsiveness was tested with a standardized mean response (SRM). Analyses of the receiver operating characteristic curves (ROCs) evaluated the sensitivity and specificity of the two methods to discriminate between clinically relevant progression and no relevant progression, using expert judgment as the gold standard (external responsiveness). Results In one year, lung involvement was stable/improved in 17 of the 45 patients (37.8%) and worsened in 28 patients (62.2%). HRCT scores changed moderately over the follow-up period. Using SFM, CaM was significantly more responsive in detecting changes due to treatment than the CoVR method. Likewise, in the analysis of the ROC curve, CaM scores showed the highest performance (AUC ROC CaM vs. CoVR, 0.951 vs. 0.807; p = 0.0065). Conclusion Quantitative analysis of CaM was more responsive than the CoVR method to accurately evaluate and monitor SSc-ILD progression or response to therapy.

Published
2020

34. Heel Pressure Injuries: Consensus-Based Recommendations for Assessment and Management

Author

Rosa Rita Zortea, Matteo Martinato, Guido Ciprandi, Diletta Olivari, Silvia Marcadelli, Massimo Rivolo, Sara Dionisi, Serena Crucianelli, Armando Gabrielli, Giovanni Pomponio, and Fabio Bellini

Subjects
Adult, 0301 basic medicine, medicine.medical_specialty, Consensus, Heel, Referral, media_common.quotation_subject, Interdisciplinary Research, Cardiology, Critical Care and Intensive Care Medicine, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Anti-Infective Agents, Jury, Comprehensive Invited Review, Multidisciplinary approach, Pressure, diabetic, medicine, Humans, Ankle Brachial Index, Child, media_common, computer.programming_language, Pressure Ulcer, Evidence-Based Medicine, business.industry, Infant, Newborn, Reproducibility of Results, Guideline, Bandages, Diabetic Foot, Test (assessment), 030104 developmental biology, Systematic review, medicine.anatomical_structure, Family medicine, Practice Guidelines as Topic, heel pressure ulcers, Emergency Medicine, neonatal/pediatric, Female, vascular assessment, business, guideline, computer, Delphi
Abstract

Significance: A systematic approach to develop experts-based recommendations could have a favorable impact on clinical problems characterized by scarce and low-quality evidence as heel pressure ulcers. Recent Advances: A systematic approach was used to conduce a formal consensus initiative. A multidisciplinary panel of experts identified relevant clinical questions, performed a systematic search of the literature, and created a list of statements. GRADE Working Group guidelines were followed. An independent international jury reviewed and voted recommendations for clinical practice. Consent was developed according to Delphi rules and GRADE method was used to attribute grade of strength. Critical Issues: The extensive search of the literature retrieved 42 pertinent articles (26 clinical studies, 7 systematic reviews or meta-analysis, 5 other reviews, 2 consensus-based articles, and 2 in vitro studies). Thirty-five recommendations and statements were created. Only 1 of 35, concerning ankle–brachial pressure index reliability in diabetic patients, was rejected by the panel. No sufficient agreement was achieved on toe brachial index test to rule out the orphan heel syndrome, removing dry eschar in adult patients without vascular impairment, and using an antimicrobial dressing in children with infected heel pressure injuries. Eleven recommendations were approved with a weak grade of strength. Experts strongly endorsed 20 recommendations. Offloading, stages I and II pressure injuries, and referral criteria were areas characterized by higher level of agreement. Future Directions: We believe that the results of our effort could improve practice, especially in areas where clear and shared opinions emerged. Barriers and limits that could hinder implementation are also discussed in the article.

Published
2020

35. Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals

Author

Carolina Benigno, Elena Bartoloni, Roberto Caporali, Maria Favaro, Chiara Tani, Armin Maier, Angela Ceribelli, M Vadacca, Carlo Salvarani, M. Meroni, Elisa Visalli, Amelia Ruffatti, Alessandra Bortoluzzi, S. Peccatori, Pier Luigi Meroni, Francesco Paolo Cantatore, Salvatore D'Angelo, Giuseppe Paolazzi, Eleonora Valentini, Gian Domenico Sebastiani, Marta Mosca, Elena Generali, Elena Baldissera, Angela Tincani, Giulia Pazzola, Véronique Ramoni, Melissa Padovan, L Zuliani, M Rodrigues, Francesca Serale, Maddalena Larosa, Cecilia Beatrice Chighizola, Rossella Reggia, Valentina Picerno, Rosario Foti, Maria Grazia Lazzaroni, Addolorata Corrado, Francesca Bellisai, Nazzarena Malavolta, Francesca Dall'Ara, Armando Gabrielli, Roberto Gerli, Cecilia Nalli, Elena De Stefani, Giorgio Pettiti, Luigi Sinigaglia, C Carini, Laura Andreoli, Maria Gerosa, Carlomaurizio Montecucco, Fabio Basta, Paola Conigliaro, Roberto Perricone, Maurizio Cutolo, I. Prevete, Corrado Campochiaro, Andrea Doria, Carlo Selmi, N Romeo, M Trevisani, Guido Valesini, Colomba Fischetti, and E Vivaldelli

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Offspring, Disease, Autoimmune Diseases, NO, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatic diseases, Pregnancy, Reproductive issues, medicine, Immunology and Allergy, Humans, Child, Prenatal exposure, Autoantibodies, 030203 arthritis & rheumatology, business.industry, Neurodevelopmental disorders, General Medicine, Maternal autoantibodies, Counselling, Reproductive Issues, 030104 developmental biology, Increased risk, Antirheumatic Agents, Childbearing age, Cohort, Female, business
Abstract

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Published
2022

36. Circulating miR-320b and miR-483-5p levels are associated with COVID-19 in-hospital mortality

Author

Angelica Giuliani, Giulia Matacchione, Deborah Ramini, Mirko Di Rosa, Anna Rita Bonfigli, Jacopo Sabbatinelli, Vladia Monsurrò, Rina Recchioni, Fiorella Marcheselli, Francesca Marchegiani, Francesco Piacenza, Maurizio Cardelli, Roberta Galeazzi, Giovanni Pomponio, Alessia Ferrarini, Armando Gabrielli, Silvia Svegliati Baroni, Marco Moretti, Riccardo Sarzani, Piero Giordano, Antonio Cherubini, Andrea Corsonello, Roberto Antonicelli, Antonio Domenico Procopio, Manuela Ferracin, Massimiliano Bonafè, Fabrizia Lattanzio, Fabiola Olivieri, Giuliani A., Matacchione G., Ramini D., Di Rosa M., Bonfigli A.R., Sabbatinelli J., Monsurro V., Recchioni R., Marcheselli F., Marchegiani F., Piacenza F., Cardelli M., Galeazzi R., Pomponio G., Ferrarini A., Gabrielli A., Svegliati Baroni S., Moretti M., Sarzani R., Giordano P., Cherubini A., Corsonello A., Antonicelli R., Procopio A.D., Ferracin M., Bonafe M., Lattanzio F., and Olivieri F.

Subjects
Male, Aging, Time Factors, Risk Assessment, Article, Predictive Value of Tests, Risk Factors, 80 and over, Humans, Circulating MicroRNA, Hospital Mortality, RNA-Seq, Aged, Aged, 80 and over, COVID-19, MiR-320b, MicroRNA, Prognosis, Up-Regulation, Hospitalization, MicroRNAs, In-hospital mortality, Female, MiR-483-5p, Biomarkers, Developmental Biology
Abstract

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.

Published
2022

37. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Author

Muriel Elhai, Nanthara Sritharan, Marouane Boubaya, Alexandra Balbir-Gurman, Elise Siegert, Eric Hachulla, Jeska de Vries-Bouwstra, Gabriela Riemekasten, Jörg H W Distler, Edoardo Rosato, Francesco Del Galdo, Fabian A Mendoza, Daniel E Furst, Carlos de la Puente, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Oliver Distler, Coralie Bloch-Queyrat, Yannick Allanore, Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Otylia Kowal Bielecka, Maurizio Cutolo, Giovanna Cuomo, Claudia Kedor, Simona Rednic, Jérome Avouac, P. Vlachoyiannopoulos, C. Montecucco, Jiri Stork, Murat Inanc, Patricia E. Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Elisabetta Zanatta, Katja Perdan-Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstrand, Mislav Radic, Yolanda Braun-Moscovici, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Madelon Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Kohm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P. Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Cristina Sobrino Grande, Øyvind Midtvedt, David Launay, Valeria Riccieri, Ruxandra Maria Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Joanna Busquets, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Percival D. Sampaio-Barros, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Mengtao Li, Walid Ahmed Abdel Atty Mohamed, Antonietta Gigante, Fahrettin Oksel, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Giuseppina Abignano, Goda Seskute, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M. Hsu, Thierry Martin, Sergey Moiseev, Lorinda S. Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Sabine Sommerlatte, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Juliana Markus, Gary R Feldman, Ana-Maria Ramazan, H.U. Scherer, Marie-Elise Truchetet, Alain Lescoat, Lorenzo Dagna, J.M. van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Mickaël Martin, Yoshiya Tanaka, Elhai, M., Sritharan, N., Boubaya, M., Balbir-Gurman, A., Siegert, E., Hachulla, E., de Vries-Bouwstra, J., Riemekasten, G., Distler, J. H. W., Rosato, E., Del Galdo, F., Mendoza, F. A., Furst, D. E., de la Puente, C., Hoffmann-Vold, A. -M., Gabrielli, A., Distler, O., Bloch-Queyrat, C., Allanore, Y., Matucci Cerinic, M., Walker, U., Iannone, F., Jordan, S., Becvar, R., Kowal Bielecka, O., Cutolo, M., Cuomo, G., Kedor, C., Rednic, S., Avouac, J., Vlachoyiannopoulos, P., Montecucco, C., Stork, J., Inanc, M., Carreira, P. E., Novak, S., Czirjak, L., Iudici, M., Kucharz, E. J., Zanatta, E., Perdan-Pirkmajer, K., Coleiro, B., Moroncini, G., Farge Bancel, D., Airo, P., Hesselstrand, R., Radic, M., Braun-Moscovici, Y., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Giollo, A., Morovic-Vergles, J., Denton, C., Vonk, M., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Hasler, P., Kohm, M., Foeldvari, I., Bajocchi, G., Salvador, M. J., Stamenkovic, B., Selmi, C. F., Tikly, M., Ananieva, L. P., Herrick, A., Muller-Ladner, U., De Palma, R., Engelhart, M., Szucs, G., Sobrino Grande, C., Midtvedt, O., Launay, D., Riccieri, V., Ionescu, R. M., Sha, A., Gheorghiu, A. M., Sunderkotter, C., Ingegnoli, F., Mouthon, L., Smith, V., Cantatore, F. P., Ullman, S., Alberto von Muhlen, C., Pozzi, M. R., Eyerich, K., Wiland, P., Vanthuyne, M., Alegre-Sancho, J. J., Herrmann, K., De Langhe, E., Anic, B., Uprus, M., Yavuz, S., Granel, B., de Souza Muller, C., Busquets, J., Agachi, S., Stebbings, S., Mathieu, D. A., Sampaio-Barros, P. D., Stamp, L., Solanki, K., Veale, D., Loyo, E., Li, M., Abdel Atty Mohamed, W. A., Gigante, A., Oksel, F., Tanaseanu, C. -M., Foti, R., Ancuta, C., Maurer, B., van Laar, J., Kayser, C., Fathi, N., Garcia de la Pena Lefebvre, P., Sibilia, J., Litinsky, I., Abignano, G., Seskute, G., Saketkoo, L. A., Kerzberg, E., Bianchi, W., Castellvi, I., Limonta, M., Rimar, D., Couto, M., Spertini, F., Marcoccia, A., Kahl, S., Hsu, I. M., Martin, T., Moiseev, S., Chung, L. S., Schmeiser, T., Majewski, D., Zdrojewski, Z., Martinez-Barrio, J., Bernardino, V., Sommerlatte, S., Levy, Y., Rezus, E., Nuri Pamuk, O., Sarzi Puttini, P., Poormoghim, H., Kotter, I., Gaches, F., Belloli, L., Sfikakis, P., Markus, J., Feldman, G. R., Ramazan, A. -M., Scherer, H. U., Truchetet, M. -E., Lescoat, A., Dagna, L., van Laar, J. M., Rudnicka, L., Oliveira, S., Atzeni, F., Kuwana, M., Mekinian, A., Martin, M., and Tanaka, Y.

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Published
2022

38. Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

Author

Simon, Kuster, Suzana, Jordan, Muriel, Elhai, Ulrike, Held, Klaus, Steigmiller, Cosimo, Bruni, Fabio, Cacciapaglia, Serena, Vettori, Elise, Siegert, Simona, Rednic, Veronica, Codullo, Paolo, Airo, Yolanda, Braun-Moscovici, Nicolas, Hunzelmann, Maria, Joao Salvador, Valeria, Riccieri, Ana-Maria, Gheorghiu, Juan José, Alegre Sancho, Katarzyna, Romanowska-Prochnicka, Ivan, Castellví, Ina, Kötter, Marie-Elise, Truchetet, F J, López-Longo, Pavel I, Novikov, Alessandro, Giollo, Yuichiro, Shirai, Laura, Belloli, Elisabetta, Zanatta, Eric, Hachulla, Vanessa, Smith, Chris, Denton, Ruxandra M, Ionescu, Tim, Schmeiser, Joerg H W, Distler, Armando, Gabrielli, Anna-Maria, Hoffmann-Vold, Masataka, Kuwana, Yannick, Allanore, Oliver, Distler, and Piercarlo Sarzi, Puttini

Subjects
Scleroderma, Systemic, Rheumatology, biological therapy, systemic sclerosis, Pulmonary Fibrosis, Immunology, Humans, Immunology and Allergy, autoimmune diseases, Propensity Score, Antibodies, Monoclonal, Humanized, United States
Abstract

ObjectivesTocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.MethodsPatients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.ResultsNinety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.ConclusionAlthough this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Published
2022

39. Impact and outcome of COVID-19 on SSc-ILD

Author

Cathrine Brunborg, Corrado Campochiaro, Francesca Tirelli, Carina Mihai, Patricia Carreira, Armando Gabrielli, Nicoletta Del Papa, Giacomo De Luca, Alessandro Giollo, M. G. Lazzaroni, Daniel E. Furst, Rosario Foti, Yannick Allanore, Paolo Airò, Madelon C. Vonk, Oliver Distler, Elisabetta Zanatta, Maria De Santis, Marco Cerinic-Matucci, Arsène Mekinian, and Anna Maria Hoffmann-Vold

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine, Intensive care medicine, business, Outcome (game theory)
Published
2021

40. Clinical and patient reported outcomes of the multidisciplinary management in patients with inflammatory bowel disease-associated spondyloarthritis

Author

Francesca Di Nicola, Antonio Di Sario, Laura Bolognini, Emanuele Bendia, Devis Benfaremo, F. Marini, Michele Maria Luchetti, Lucia Perini, Giammarco Fava, Monia Ciferri, Giovanni Pomponio, L. Manfredi, Valentina Marconi, Armando Gabrielli, Antonio Benedetti, and Piergiorgio Mosca

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Arthritis, 030204 cardiovascular system & hematology, Inflammatory bowel disease, Workflow, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Quality of life, Multidisciplinary approach, Internal medicine, Spondylarthritis, Internal Medicine, medicine, Humans, In patient, Patient Reported Outcome Measures, 030212 general & internal medicine, Medical prescription, Patient Care Team, Biological Products, business.industry, Articular disease, Remission Induction, Middle Aged, medicine.disease, digestive system diseases, Treatment Outcome, Gastrointestinal disease, Antirheumatic Agents, Critical Pathways, Quality of Life, Colitis, Ulcerative, Female, business
Abstract

Objective Arthritis is the most frequent extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). The coexistence of intestinal and articular inflammation advocates the need for a multidisciplinary management of patients with IBD-associated spondyloarthritis. Methods Consecutive IBD patients were evaluated jointly by the gastroenterologist and the rheumatologist in a combined clinic. All the patients were assessed and screened for articular involvement, disease activity and health related quality of life. After the prescription of a shared treatment, patients with spondyloarthritis were followed up for 24 months. Results Two hundred sixty-two IBD patients, including 80 who were classified as affected by spondyloarthritis according to the ASAS criteria, were included in the study. At baseline, patients with both IBD and spondyloarthritis showed worse quality of life in both the physical and mental domains. The multidisciplinary management provided a significant improvement of gastrointestinal and articular manifestations, as well as the health-related quality of life. Moreover, global and gastrointestinal-specific quality of life significantly correlated with articular disease activity. Conclusion The multidisciplinary management significantly improves both articular and gastrointestinal disease activities and the quality of life of patients with IBD-associated spondyloarthritis. An appropriate screening strategy and the integrated management of these patients should be encouraged and employed in clinical practice.

Published
2019

42. Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort

Author

Maria Letizia Urban, Enrico Brunetta, Giuseppe A. Ramirez, Francesco Benvenuti, Giacomo Emmi, Giulia Pazzola, Michela Gasparotto, Elena Bartoloni, Mariele Gatto, Elisa Gremese, Micaela Fredi, Maria Gerosa, Paolo Cardinaletti, Francesco Ciccia, Giovanni Orsolini, Marta Mosca, Amato de Paulis, Luca Iaccarino, Paola Faggioli, Enrica Bozzolo, Tania Ubiali, Fulvia Ceccarelli, Alessandra Bortoluzzi, Fabrizio Conti, Antonella Laria, Serena Fasano, Chiara Tani, Salvatore Scarpato, Angela Tincani, Marcello Govoni, Laura Andreoli, Carlo Salvarani, Roberto Gerli, Francesca Regola, Maddalena Larosa, Francesca Wanda Rossi, Armando Gabrielli, Ginevra De Marchi, Margherita Zen, Luca Petricca, Francesca Saccon, Maurizio Rossini, Valentina Canti, Salvatore De Vita, Andrea Doria, Gatto, M., Saccon, F., Andreoli, L., Bartoloni, E., Benvenuti, F., Bortoluzzi, A., Bozzolo, E., Brunetta, E., Canti, V., Cardinaletti, P., Ceccarelli, F., Ciccia, F., Conti, F., De Marchi, G., de Paulis, A., De Vita, S., Emmi, G., Faggioli, P., Fasano, S., Fredi, M., Gabrielli, A., Gasparotto, M., Gerli, R., Gerosa, M., Govoni, M., Gremese, E., Laria, A., Larosa, M., Mosca, M., Orsolini, G., Pazzola, G., Petricca, L., Ramirez, G. A., Regola, F., Rossi, F. W., Rossini, M., Salvarani, C., Scarpato, S., Tani, C., Tincani, A., Ubiali, T., Urban, M. L., Zen, M., Doria, A., and Iaccarino, L.

Subjects
Male, Settore MED/16 - REUMATOLOGIA, Lupus nephritis, Kidney, Gastroenterology, Renal response, Cohort Studies, chemistry.chemical_compound, Immunosuppressive Agent, Monoclonal, B-Cell Activating Factor, Immunology and Allergy, Lupus Erythematosus, Systemic, Humanized, Proteinuria, Systemic lupus erythematosus, Standard treatment, Middle Aged, Lupus Nephritis, Treatment Outcome, Italy, Cohort, Belimumab, Adult, Antibodies, Monoclonal, Humanized, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Immunosuppressive Agents, medicine.symptom, medicine.drug, Human, medicine.medical_specialty, Immunology, Renal function, Antibodies, NO, Follow-Up Studie, Internal medicine, medicine, Creatinine, Lupus Erythematosus, business.industry, Lupus nephriti, Systemic, medicine.disease, chemistry, Cohort Studie, business
Abstract

Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria

Published
2021

43. Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients

Author

Marco Moretti, Silvia Baroni, Giovanni Pomponio, Antonio Domenico Procopio, Giulia Matacchione, Fabiola Olivieri, Manuela Ferracin, Marianna Pavani, Massimiliano Bonafè, Noemi Laprovitera, Angelica Giuliani, Alessia Ferrarini, Jacopo Sabbatinelli, Silvia Latini, Armando Gabrielli, Sabbatinelli J., Giuliani A., Matacchione G., Latini S., Laprovitera N., Pomponio G., Ferrarini A., Svegliati Baroni S., Pavani M., Moretti M., Gabrielli A., Procopio A.D., Ferracin M., Bonafè M., and Olivieri F.

Subjects
0301 basic medicine, Male, Aging, chemistry.chemical_compound, 0302 clinical medicine, Global health, Medicine, media_common, biology, microRNA, Tocilizumab, Middle Aged, Biomarker (medicine), Female, medicine.symptom, Human, Drug, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), media_common.quotation_subject, Inflammation, Antibodies, Monoclonal, Humanized, Article, 03 medical and health sciences, Internal medicine, Humans, Circulating MicroRNA, Interleukin 6, Pandemics, Aged, Pandemic, business.industry, SARS-CoV-2, interleukin-6, COVID-19, Biomarker, Inflammaging, COVID-19 Drug Treatment, Clinical trial, MicroRNAs, Ageing, 030104 developmental biology, chemistry, biology.protein, business, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

Highlights • Tocilizumab (TCZ) is currently being tested in COVID‐19‐induced cytokine storm. • COVID-19 patients responding to TCZ have higher post-treatment levels of circulating miR-146a. • Low levels of miR-146a are associated with death in COVID-19 patients not responding to TCZ. • MicroRNAs can represent biomarkers of response to anti-inflammatory interventions in COVID-19., Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. The most amount of the death toll is accounted by old people affected by age-related diseases that develop a hyper-inflammatory syndrome. In this regard, we hypothesized that COVID-19 severity may be linked to inflammaging. Here, we examined 30 serum samples from patients enrolled in the clinical trial NCT04315480 assessing the clinical response to a single-dose intravenous infusion of the anti-IL-6 receptor drug Tocilizumab (TCZ) in COVID-19 patients with multifocal interstitial pneumonia. In these serum samples, as well as in 29 age- and gender-matched healthy control subjects, we assessed a set of microRNAs that regulate inflammaging, i.e. miR-146a-5p, miR-21-5p, and miR-126-3p, which were quantified by RT-PCR and Droplet Digital PCR. We showed that COVID-19 patients who did not respond to TCZ have lower serum levels of miR-146a-5p after the treatment (p = 0.007). Among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p = 0.008). Our data show that a blood-based biomarker, such as miR-146a-5p, can provide clues about the molecular link between inflammaging and COVID-19 clinical course, thus allowing to better understand the use of biologic drug armory against this worldwide health threat.

Published
2021
Full Text
View/download PDF

44. Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease-Associated spondyloarthritis

Author

Andrea Costantini, Devis Benfaremo, Chiara Avellini, Armando Gabrielli, Antonio Benedetti, Piergiorgio Mosca, Aroldo Rizzo, Francesco Ciccia, Michele Maria Luchetti, Silvia Svegliati, Tatiana Spadoni, Monica Mattioli Belmonte Cima, Monia Ciferri, Nadia Viola, Alfredo Santinelli, Antonella Berretta, Daniela Marzioni, Luchetti, M. M., Ciccia, F., Avellini, C., Benfaremo, D., Rizzo, A., Spadoni, T., Svegliati, S., Marzioni, D., Santinelli, A., Costantini, A., Viola, N., Berretta, A., Ciferri, M., Mattioli Belmonte Cima, M., Mosca, P., Benedetti, A., and Gabrielli, A.

Subjects
0301 basic medicine, Lipopolysaccharides, T cell, Lipopolysaccharide Receptors, Inflammation, Gut flora, Systemic inflammation, Fatty Acid-Binding Proteins, digestive system, Monocytes, Pathogenesis, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, soluble biomarker, Ileum, inflammatory bowel disease, Spondylarthritis, medicine, Humans, Pharmacology (medical), Intestinal Mucosa, Adaptor Proteins, Signal Transducing, 030203 arthritis & rheumatology, Osteoblasts, biology, business.industry, dysbiosi, spondyloarthritis, biology.organism_classification, medicine.disease, Inflammatory Bowel Diseases, epithelial intestinal impairment, Gut Epithelium, 030104 developmental biology, medicine.anatomical_structure, Bacterial Translocation, Case-Control Studies, Immunology, medicine.symptom, business, Dysbiosis, Biomarkers
Abstract

Objectives Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients. Methods Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line. Results Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells. Conclusion SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.

Published
2021

45. Gastric Antral Vascular Ectasia (GAVE)

Author

Armando Gabrielli, Devis Benfaremo, and L. Manfredi

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, business.industry, Anemia, Stomach, medicine.medical_treatment, Gastric antral vascular ectasia, Hematopoietic stem cell transplantation, medicine.disease, Pylorus, Gastroenterology, medicine.anatomical_structure, Internal medicine, Vascular Disorder, Medicine, business, Antrum
Abstract

Gastric antral vascular ectasia (GAVE), or watermelon stomach, is a rare acquired vascular disorder, characterized by multiple longitudinal stripes of red vessels originating from the pylorus and involving the antrum. In recent years, GAVE emerged as a potential gastrointestinal complication in patients with systemic sclerosis, with an estimated prevalence that ranges between 1% and 22.3%. GAVE usually presents with a refractory iron-deficiency anemia, that may require repeated blood transfusions, due to recurring gastrointestinal bleeding. Given the close association between GAVE and anti-RNA polymerase III antibodies, screening these high risk patients with endoscopy should be considered even in absence of anemia or gastric-related symptoms. Endoscopic methods, including thermal and mechanical techniques, are the treatment of choice for GAVE-related bleeding. In patients with GAVE and systemic sclerosis that are refractory to endoscopic therapy, cyclophosphamide and autologous hematopoietic stem cell transplantation may be an effective treatment option.

Published
2020

46. Risk of acute arterial and venous thromboembolic events in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)

Author

Alfredo Vannacci, Christian Dejaco, Carlo Manno, Paolo Fraticelli, Elisa Tinazzi, Giacomo Emmi, Giuseppe Paolazzi, Roberto Bortolotti, Paolo Fabbrini, Paolo Delvino, Johann Willeit, Matteo Piga, Angela Padula, Giuseppe Lopalco, Marco Pellecchio, Franco Franceschini, Armando Gabrielli, Pietro Leccese, Lorenzo Delfino, Mara Felicetti, Federica Maritati, Guido Jeannin, Vito Racanelli, Milena Bond, Simone Negrini, Federico Alberici, Peter Willeit, Stefano Polti, Maria Rita Marchi, Roberto Padoan, Franco Schiavon, Alvise Berti, Giulia Pazzola, Loredana Colla, Paola Tomietto, Augusto Vaglio, Paola Toniati, Iuliana Badiu, Sara Monti, Roberto Caporali, Chiara Marvisi, Giuseppe Guida, Savino Sciascia, Enrica Bozzolo, Adriana Cariddi, Domenico Prisco, Iacopo Olivotto, Claudio Lunardi, Fabrizio Conti, Lorenzo Dagna, Alberto Cauli, Luca Quartuccio, Renato Alberto Sinico, Alessandra Palmisano, Florenzo Iannone, Maria Letizia Urban, Silvia Tamanini, Alessandra Bortoluzzi, Roberta Priori, Carlomaurizio Montecucco, Vincenzo Venerito, Federica Furini, Gina Gregorini, Alessandra Bettiol, Carlo Selmi, Martina Tedesco, Angelo Vacca, Carlo Salvarani, Gabriella Moroni, Giovanni Rolla, Marcello Govoni, Silvano Bettio, Maria Rosa Pozzi, and Stefan Kiechl

Subjects
medicine.medical_specialty, education.field_of_study, Proportional hazards model, business.industry, Population, Birmingham Vasculitis Activity Score, Lower risk, medicine.disease, Internal medicine, Cohort, Eosinophilic, medicine, Granulomatosis with polyangiitis, education, business, Cohort study
Abstract

Background and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

Published
2020

47. Incidence and predictors of arrhythmias in patients with systemic sclerosis and no overt cardiac disease

Author

Giulia Stronati, L. Manfredi, A Dello Russo, C Dichiara, Federico Guerra, and Armando Gabrielli

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Incidence (epidemiology), cardiovascular system, medicine, In patient, Disease, Cardiology and Cardiovascular Medicine, business
Abstract

Background Cardiac involvement in SSc is frequent, mostly subclinical and represents a negative prognostic factor. Speckle tracking derived measurement global longitudinal strain (GLS) has been able to identify primary heart involvement in patients with SSc and no overt cardiac disease. SSc-related cardiomyopathy, defined as a condition affecting the heart primarily and globally, has been proven to progress over time and seems to be correlated to cardiac arrhythmias. Nonetheless, cardiac arrhythmias represent 6% of the overall causes of death in SSc patients. Purpose The aim of our study was to assess the incidence of cardiac arrhythmias in SSc patients with no overt cardiac disease and to identify potential predictors. Methods Prospective longitudinal study enrolling all consecutive patients with a diagnosis of SSc and no overt cardiac disease or pulmonary hypertension. Echocardiographic parameters and GLS were obtained at baseline and at each follow up. Presence of atrial fibrillation (AF), atrial tachycardia (AT), ventricular ectopic beats >1000/24 h (VEB), supraventricular ectopic beats (SVEB), bundle branch block (BBB) and atrioventricular block (AVB) was assessed through clinical history, ECG and 24-Holter monitoring over time. Results Among 67 consecutive patients with SSc, 11 (16.7%) had at least one episode of AF or AT. Moreover, respectively 12 (17.9%) and 16 (23.9%) had a significant amount of SVEB and VEB at Holter monitoring. Conduction defects were common, with 4 (4.6%) of all patients with grade I AVB, 1 (1.5%) with grade II AVB and 1 (1.5%) with complete heart block. Complete right BBB was seen in 6 (6.9%) of patients. Four patients (4.6%) experienced a sudden cardiac death during follow-up (median 20 months, 1st-3rd quartile 12–24 months). Years from SSc diagnosis (RR 1.10; 95% CI 1.02–1.23; p=0.047) and indexed right atrial volume (iRAV; RR 1.22; 95% CI 1.07–1.39; p=0.004), but not indexed left atrial volume were independently correlated with the diagnosis of AF/AT. The same two variables were independently correlated with any degree of AV block (years from SSc diagnosis: RR 1.11; 95% CI 1.01–1.23; p=0.004; iRAV: RR 1.14; 95% CI 1.02–1.27; p=0.019). Due to the low sample size, we were unable to detect any clinical predictors of sudden cardiac death in our population, however those who died experienced a larger worsening in left ventricle GLS values (4.0±1.6 vs. 0.9±0.4, p=0.056). Conclusions Supraventricular arrhythmias and conduction defects are common in patients with SSc. Time from diagnosis and right atrial volumes are able to predict the incidence of such conditions, supporting the hypothesis that a long-lasting disease and the anatomical remodelling of the right atrium could contribute to the developing of tachy- and bradyarrhythmias in this population. Funding Acknowledgement Type of funding source: None

Published
2020

48. The power of the EUSTAR cohort: key findings to date and implications for management of systemic sclerosis patients

Author

Jérôme Avouac, Francesco Benvenuti, Elisabetta Zanatta, Yannick Allanore, Armando Gabrielli, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Ulf Müller-Ladner, Oliver Distler, Franco Cozzi, Andrea Doria, and University of Zurich

Subjects
medicine.medical_specialty, systemic sclerosis, Immunology, EUSTAR, disease activity, epidemiology, general management, prognostic factors, recent insights, therapy, 610 Medicine & health, Disease, Therapeutic approach, Quality of life (healthcare), Fibrinolytic Agents, Epidemiology, medicine, Immunology and Allergy, Humans, Vasoconstrictor Agents, Precision Medicine, skin and connective tissue diseases, Intensive care medicine, Scleroderma, Systemic, integumentary system, business.industry, 10051 Rheumatology Clinic and Institute of Physical Medicine, Precision medicine, Prognosis, Clinical trial, Clinical research, Early Diagnosis, Databases as Topic, Cohort, Quality of Life, business, Immunosuppressive Agents
Abstract

The rarity of systemic sclerosis (SSc) and its widely heterogeneous presentation and disease course are the main limitations for clinical research. The European Scleroderma Trials and Research group (EUSTAR) was launched in 2004, aiming to unify research efforts in the field of SSc. The central EUSTAR database has grown exponentially over the years, promoting new research and clinical trials, shedding new light on SSc diagnosis, its clinical course and providing new ideas for state-of-the-art therapy.Areas covered: The authors summarized key findings of the main EUSTAR studies by reviewing PubMed and Web-of-Science databases through July 2020. The authors focused on the very early diagnosis of SSc, the prediction of disease course and mortality, the evaluation of disease activity and quality of life, the general management and therapy.Expert opinion: The findings elucidated in EUSTAR studies have substantially improved the diagnostic and therapeutic approach to SSc in the last fifteen years. Further efforts are warranted to identify early prognostic markers of the disease and stratify patients who may benefit most from vasoactive, immunosuppressive, and/or antifibrotic therapy. This will be particularly important in leading the future of SSc towards precision medicine and to promote more targeted clinical trials.

Published
2020

49. Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact

Author

Martina Bonifazi, Nicola Sverzellati, Eva Negri, Joseph Jacob, Ryoko Egashira, Sara Piciucchi, Federico Mei, Angelo De Lauretis, Dina Visca, Nicole Goh, Matteo Bonini, Carlo La Vecchia, Felix Chua, Vasileios Kouranos, George Margaritopoulos, Maria Kokosi, Toby M Maher, Stefano Gasparini, Armando Gabrielli, Athol U Wells, and Elisabetta Renzoni

Published
2020

50. Tocilizumab in Covid-19 Interstitial Pneumonia: A Phase II Pilot Study

Author

Donatella Amico, Federico Mei, Marcello Mario D’Errico, Stefano Menzo, Laura Morbidoni, Marco B. L. Rocchi, Vincenzo G Menditto, Giovanni Pomponio, Marco Moretti, Alessia Ferrarini, Aldo Salvi, Gabriele Frausini, Abele Donati, Silvia Svegliati, Armando Gabrielli, Lina Zuccatosta, Marcello Tavio, Andrea Giacometti, Giancarlo Titolo, Maicol Onesta, Marianna Pavani, and Martina Bonifazi

Subjects
medicine.medical_specialty, chemistry.chemical_compound, Tocilizumab, Coronavirus disease 2019 (COVID-19), chemistry, business.industry, Internal medicine, Phase (matter), medicine, Interstitial pneumonia, business, Gastroenterology
Abstract

Background: Multiple studies have been conducted to investigate Tocilizumab in patients with cOVID-19 pneumonitis. However, published reports show conflicting results, largely due to weak retrospective designs and heterogeneity in critical methodological issues.Methods: This open-label trial was structured according to the Simon’s optimal two-stage design in order to clarify which patients could really benefit from anti-IL6 strategies and how a future randomized trial should be designed to provide reliable and unequivocal results. 46 patients received a single infusion of Tocilizumab. Inclusion criteria were: SARS-CoV2 infection diagnosed by rt-PCR, multifocal interstitial pneumonia, need of oxygen therapy (FiO2 50%) to maintain SO2 >93%, recent (within the last 24 hours) worsening of lung function. Clinical outcomes were established a priori to assess whether a patient responded to treatment. A low number of carefully chosen clinical and biological markers was measured in order to test their predictive values. Primary end point was early and sustained clinical response. Results: Twenty-one (46%) patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 hours after tocilizumab infusion (p=0.049) and higher baseline values of PaO2/FiO2 (p=0.008) predicted a favorable clinical response. Patients not improving at 72 hours were also non-responder at day 7. 11/25 of non-responder patients were intubated and 7 died. High levels of vWF were detected in all sera, with a tendency towards higher concentrations in the non-responder group. Conclusions: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in selected patients with severe COVID-19 pneumonitis warrants investigations in randomized trials. Trial registration: NCT 04315480

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results