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1. Experimental Pharmacotherapy for Dry Eye Disease: A Review

Author

Baiula M and Spampinato S

Subjects
dry eye disease, inflammation, tivanisiran, il-1r antagonist, skq1, Therapeutics. Pharmacology, RM1-950
Abstract

Monica Baiula, Santi Spampinato Department of Pharmacy and Biotechnology, University of Bologna, Bologna, ItalyCorrespondence: Santi SpampinatoDepartment of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, Bologna, ItalyTel +39 0512091851Email santi.spampinato@unibo.itAbstract: Dry eye disease (DED) is a complex multifactorial disease showing heterogenous symptoms, including dryness, photophobia, ocular discomfort, irritation and burning but also pain. These symptoms can affect visual function leading to restrictions in daily life activities and reduction in work productivity with a consequently high impact on quality of life. Several pathological mechanisms contribute to the disease: evaporative water loss leads to impairment and loss of tear homeostasis inducing either directly or indirectly to inflammation, in a self-perpetuating vicious cycle. Dysregulated ocular immune responses result in ocular surface damage, which further contributes to DED pathogenesis. Currently, DED treatment is based on a flexible stepwise approach to identify the most beneficial intervention. Although most of the available treatments may control to a certain extent some signs and symptoms of DED, they show significant limitations and do not completely address the needs of patients suffering from DED. This review provides an overview of the emerging experimental therapies for DED. Several promising therapeutic strategies are under development with the aim of dampening inflammation and restoring the homeostasis of the ocular surface microenvironment. Results from early phase clinical trials, testing the effects of EnaC blockers, TRPM8 agonist or mesenchymal stem cells in DED patients, are especially awaited to demonstrate their therapeutic value for the treatment of DED. Moreover, the most advanced experimental strategies in the pipeline for DED, tivanisiran, IL-1R antagonist EBI-005 and SkQ1, are being tested in Phase III clinical trials, still ongoing. Nevertheless, although promising results, further studies are still needed to confirm efficacy and safety of the new emerging therapies for DED.Keywords: dry eye disease, inflammation, tivanisiran, IL-1R antagonist, SkQ1

Published
2021

3. USE DOSE OF SURFACE MAPS TO IDENTIFY BLADDER SUB-REGIONS ASSOCIATED WITH LATE TOXICITIES AFTER PROSTATE CANCER RADIOTHERAPY

Author

Gioscio, E., primary, Cicchetti, A., additional, Iacovacci, J., additional, Spampinato, S., additional, Avuzzi, B., additional, Chiorda, B. Noris, additional, Badenchini, F., additional, Waskiewicz, J.M., additional, Garibaldi, E., additional, Villa, E., additional, Magli, A., additional, Cante, D., additional, Girelli, G., additional, Gatti, M., additional, Farella, L., additional, Ferrari, P., additional, Piva, C., additional, Pavarini, M., additional, Valdagni, R., additional, Vavassori, V., additional, Munoz, F., additional, Fiorino, C., additional, Cozzarini, C., additional, and Rancati, T., additional

Published
2023
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4. ASSOCIATION OF PERSISTENT URINARY SYMPTOMS WITH QUALITY OF LIFE AFTER PROSTATE CANCER RADIOTHERAPY

Author

Spampinato, S., primary, Waskiewicz, J.M., additional, Avuzzi, B., additional, Garibaldi, E., additional, Faiella, A., additional, Villa, E., additional, Magli, A., additional, Cante, D., additional, Girelli, G., additional, Gatti, M., additional, Chiorda, B. Noris, additional, Rago, L., additional, Ferrari, P., additional, Piva, C., additional, Pavarini, M., additional, Rancati, T., additional, Valdagni, R., additional, Vavassori, V., additional, Munoz, F., additional, Sanguineti, G., additional, Di Muzio, N., additional, Kirchheiner, K., additional, Fiorino, C., additional, and Cozzarini, C., additional

Published
2023
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5. Association between Regular Vaginal Dilation and/or Sexual Activity and Long-Term Vaginal Morbidity in Cervical Cancer Survivors

Author

Kirchheiner, K., primary, Zaharie, A.T., additional, Smet, S., additional, Spampinato, S., additional, Chargari, C., additional, Mahantshetty, U.M., additional, Segedin, B., additional, Bruheim, K., additional, Rai, B., additional, Cooper, R., additional, Van der Steen-Banasik, E., additional, Wiebe, E.M., additional, Potter, R., additional, Kirisits, C., additional, Schmid, M., additional, Haie-Meder, C., additional, Tanderup, K., additional, De Leeuw, A., additional, Jurgenliemk-Schulz, I., additional, and Nout, R.A., additional

Published
2023
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9. OC-0129 Impact of brachytherapy applicator on morbidity and local control in cervix cancer: EMBRACE study

Author

Serban, M., primary, Spampinato, S., additional, de Leeuw, A., additional, Fortin, I., additional, Nevascil, N., additional, Kirisits, C., additional, Schmid, M., additional, Mahantshetty, U., additional, Hoskin, P., additional, Segedin, B., additional, Bruheim, K., additional, Huang, F., additional, Pieters, B., additional, Nout, R., additional, Pötter, R., additional, Kirchheiner, K., additional, Jürgenliemk-Schulz, I., additional, and Tanderup, K., additional

Published
2023
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12. PO-1483 Persistent urinary symptoms and long-term quality of life after prostate cancer radiotherapy

Author

Spampinato, S., primary, Waskiewicz, J.M., additional, Avuzzi, B., additional, Garibaldi, E., additional, Faiella, A., additional, Villa, E., additional, Magli, A., additional, Cante, D., additional, Girelli, G., additional, Gatti, M., additional, Ferella, L., additional, Noris Chiorda, B., additional, Rago, L., additional, Ferrari, P., additional, Piva, C., additional, Maddalena, P., additional, Tiziana, R., additional, Valdagni, R., additional, Vavassori, V., additional, Munoz, F., additional, Sanguineti, G., additional, Di Muzio, N., additional, Kirchheiner, K., additional, Fiorino, C., additional, and Cozzarini, C., additional

Published
2023
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15. CO-03.1 - USE DOSE OF SURFACE MAPS TO IDENTIFY BLADDER SUB-REGIONS ASSOCIATED WITH LATE TOXICITIES AFTER PROSTATE CANCER RADIOTHERAPY

Author

Gioscio, E., Cicchetti, A., Iacovacci, J., Spampinato, S., Avuzzi, B., Chiorda, B. Noris, Badenchini, F., Waskiewicz, J.M., Garibaldi, E., Villa, E., Magli, A., Cante, D., Girelli, G., Gatti, M., Farella, L., Ferrari, P., Piva, C., Pavarini, M., Valdagni, R., Vavassori, V., Munoz, F., Fiorino, C., Cozzarini, C., and Rancati, T.

Published
2023
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16. Using machine learning for the classification of Seismic Signals at Vulcano, Italy

Author

Falsaperla, S., Ferrari, F., Langer, H., and Spampinato, S.

Abstract

A Vulcanian eruption is described as an eruptive style with strong explosive characteristics. The name derives from the island of Vulcano in Italy, the first place in which it was observed during the last eruptive activity between 1888 and 1890.In this paper we analyze the seismicity recorded at Vulcano during a seismic unrest starting in September 2021 and still present as of November 2022. The distinctive feature of this seismicity is the presence of a variety of signals, most of which have a very long period (~0.5 s) signature. Low frequency content is interpreted as due to fluid involvement. Therefore, the high occurrence rate of VLP seismicity is a potential indication of pressure buildup within the volcanic system, and may herald phreatomagmatic activity (usually the first stage of a Vulcanian eruption), with serious consequences for inhabitants and tourists.Our analyses exploit machine learning procedures, with particular reference to pattern classification, at the aim of identifying varying classes of seismic events and trace their evolution over time. This classification can be useful for surveillance purposes contributing, along with other early warning methods, to reduce the devastating consequences of eruptions for people and property., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2023
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17. Mapracorat, a selective glucocorticoid receptor agonist, causes apoptosis of eosinophils infiltrating the conjunctiva in late-phase experimental ocular allergy

Author

Baiula M, Bedini A, Baldi J, Cavet ME, Govoni P, and Spampinato S

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Monica Baiula,1 Andrea Bedini,1 Jacopo Baldi,1 Megan E Cavet,2 Paolo Govoni,3 Santi Spampinato11Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; 2Global Pharmaceutical R&D, Bausch & Lomb Inc., Rochester, NY, USA; 3Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, ItalyBackground: Mapracorat, a novel nonsteroidal selective glucocorticoid receptor agonist, has been proposed for the topical treatment of inflammatory disorders as it binds with high affinity and selectivity to the human glucocorticoid receptor and displays a potent anti-inflammatory activity, but seems to be less effective in transactivation of a number of genes, resulting in a lower potential for side effects. Contrary to classical glucocorticoids, mapracorat displays a reduced ability to increase intraocular pressure and in inducing myocilin, a protein linked to intraocular pressure elevation. Allergic conjunctivitis is the most common form of ocular allergy and can be divided into an early phase, developing immediately after allergen exposure and driven primarily by mast cell degranulation, and a late phase, developing from 6–10 hours after the antigen challenge, and characterized by conjunctival infiltration of eosinophils and other immune cells as well as by the production of cytokines and chemokines.Methods: In this study, mapracorat was administered into the conjunctival sac of ovalbumin (OVA)-sensitized guinea pigs 2 hours after the induction of allergic conjunctivitis, with the aim of investigating its activity in reducing clinical signs of the late-phase ocular reaction and to determine its mechanism of anti-allergic effects with respect to apoptosis of conjunctival eosinophils and expression of the chemokines C-C motif ligand 5 (CCL5), C-C motif ligand 11 (CCL11), and interleukin-8 (IL-8) and the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).Results: Mapracorat, administered into the conjunctival sac of OVA-sensitized guinea pigs 2 hours after allergen exposure, was effective in reducing clinical signs, eosinophil infiltration, and eosinophil peroxidase activity in the guinea pig conjunctiva; furthermore, it reduced conjunctival mRNA levels and protein expression of both CCL5 and CCL11. Mapracorat was more effective than dexamethasone in increasing, in conjunctival sections of OVA-treated guinea pigs, apoptotic eosinophils.Conclusion: Mapracorat displays anti-allergic properties in controlling the late phase of ocular allergic conjunctivitis and is a promising candidate for the topical treatment of allergic eye disorders.Keywords: allergic conjunctivitis, late-phase response, eosinophil

Published
2014

18. OC-0503 Effect of dose and fractionation de-escalation in low-risk cervix cancer treated with EBRT and BT

Author

Serban, M., Gallois, M., Urtubey, T., Nout, R., de Leeuw, A., Fokdal, L., Assenholt, M., Spampinato, S., Bruheim, K., Segedin, B., Chopra, S., Schmid, M., Nesvacil, N., Ecker, S., Kirchheiner, K., Pötter, R., Westerveld, H., Huang, F., Velema, L., Tan, L.T., Valgma, M., Mathiesen, H., Lindegaard, J., Jürgenliemk-Schulz, I., and Tanderup, K.

Published
2022
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19. OC-0588 Impact of persistent symptoms on long-term quality of life of cervical cancer survivors in EMBRACE I

Author

Spampinato, S., primary, Tanderup, K., additional, Nout, R., additional, Smet, S., additional, Lindegaard, J.C., additional, Fokdal, L.U., additional, Pötter, R., additional, Sturdza, A., additional, Segedin, B., additional, Jürgenliemk-Schulz, I., additional, Bruheim, K., additional, Mahantshetty, U., additional, Chargari, C., additional, Rai, B., additional, Cooper, R., additional, van der Steen-Banasik, E., additional, Sundset, M., additional, Wiebe, E., additional, Villafranca, E., additional, Van Limbergen, E., additional, Chopra, S., additional, and Kirchheiner, K., additional

Published
2022
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21. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study

Author

Pötter R., Tanderup K., Schmid M.P., Jürgenliemk-Schulz I., Haie-Meder C., Fokdal L.U., Sturdza A.E., Hoskin P., Mahantshetty U., Segedin B., Bruheim K., Huang F., Rai B., Cooper R., van der Steen-Banasik E., Van Limbergen E., Pieters B.R., Tan L.-T., Nout R.A., De Leeuw A.A.C., Ristl R., Petric P., Nesvacil N., Kirchheiner K., Kirisits C., Lindegaard J.C., Chargari C., Dumas I., Lowe G., Swamidas J., Hudej R., Paulsen Hellebust T., Menon G., Oinam A.S., Bownes P., Christiaens M., De Brabandere M., Janssen H., Oosterveld B., Koedooder K., Langeland Marthinsen A.B., Sundset M., Whitney D., Ketelaars M., Lutgens L.C.H.W., Reinniers B., Mora I., Villafranca E., Antal G., Hadjiev J., Bachand F., Batchelar D., Erickson B., Rownd J., Jacobson G., Kim Y., Anttila M., Palmgren J.-E., An J., Assenholt M.S., Banerjee S., Bentzen S., Berger T., Dankulchai P., Diendorfer T., Dilworth I., Dimopoulos J., Dörr E., Ecker S., Federico M., Fidarova E., Fortin I., Georg P., Gora J., Hegazy N., Jastaniyah N., Jensen N.B.K., Liederer T., Majercakova K., Misimovic D., Motisi L., Najjari Jamal D., Nkiwane K., Schwartz-Vittrup A., Serban M., Smet S., Spampinato S., Trnkova P., Valgma M., Westerveld H., Wong J.S.Y., Yoshida K., and EMBRACE Collaborative Group

Subjects
Asia, diagnostic imaging, Brachytherapy, cisplatin, uterine cervix carcinoma, morbidity, image guided radiotherapy, external beam radiotherapy, Article, Disease-Free Survival, multiple cycle treatment, chemoradiotherapy, volumetric modulated arc therapy, cancer control, fistula, follow up, urogenital tract disease, International Federation of Gynecology and Obstetrics, uterine cervix tumor, human, procedures, nuclear magnetic resonance imaging, outcome assessment, disease free survival, lymph node metastasis, cancer staging, adult, clinical trial, cohort analysis, major clinical study, intensity modulated radiation therapy, Europe, aged, multicenter study, female, quality of life, priority journal, North America, observational study, pathology, conformal radiotherapy, radiation dose, image guided adaptive brachytherapy, uterine cervix cancer, prospective study
Abstract

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems. © 2021 Elsevier Ltd

Published
2021
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22. OC-0296 Risk factors for severe gastrointestinal morbidity in locally advanced cervix cancer (EMBRACE study)

Author

Spampinato, S., primary, Jensen, N.B., additional, Fokdal, L.U., additional, Pötter, R., additional, Haie-Meder, C., additional, Lindegaard, J.C., additional, Schmid, M.P., additional, Sturdza, A., additional, Jürgenliemk-Schulz, I.M., additional, Mahantshetty, U., additional, Segedin, B., additional, Hoskin, P., additional, Bruheim, K., additional, Rai, B., additional, Wiebe, E., additional, Cooper, R., additional, van der Steen-Banasik, E., additional, Van Limbergen, E., additional, Kirisits, C., additional, Nout, R.A., additional, Chopra, S., additional, Kirchheiner, K., additional, and Tanderup, K., additional

Published
2021
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28. OC-0569: Incidence of severe gastrointestinal and urinary fistulas, bleeding and strictures: EMBRACE results

Author

Vittrup, A.S., primary, Kirchheiner, K., additional, Tanderup, K., additional, Jensen, N.B.K., additional, Spampinato, S., additional, Fokdal, L.U., additional, Kirisits, C., additional, Haie-Meder, C., additional, Lindegaard, J.C., additional, Schmid, M., additional, Sturdza, A., additional, Mahantshetty, U., additional, Jürgenliemk-Schulz, I.M., additional, Hoskin, P., additional, Segedin, B., additional, Bruheim, K., additional, Rai, B., additional, Wiebe, E., additional, Van der Steen-Banasik, E., additional, Cooper, R., additional, Van Limbergen, E., additional, Sundset, M., additional, Pieters, B.R., additional, Nout, R., additional, and Pötter, R., additional

Published
2020
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29. OC-1049: Dose-effect relationship between vaginal dose points and vaginal stenosis in cervical cancer

Author

Westerveld, H., primary, Kirchheiner, K., additional, Nout, R.A., additional, Tanderup, K., additional, Lindegaard, J.C., additional, Spampinato, S., additional, Sturdza, A., additional, Nesvacil, N., additional, Bruheim, K., additional, Hellebust, T.P., additional, Pieters, B.R., additional, Jürgenliemk-Schulz, I.M., additional, Pötter, R., additional, and De Leeuw, A., additional

Published
2020
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30. OC-0317: Risk factors for persistent late fatigue after radiochemotherapy in cervical cancer (EMBRACE study)

Author

Smet, S., primary, Tanderup, K., additional, Nout, R., additional, Jürgenliemk-Schulz, I., additional, Spampinato, S., additional, Chargari, C., additional, Lindegaard, J., additional, Mahantshetty, U., additional, Strudza, A., additional, Schmid, M., additional, Hoskin, P., additional, Segedin, B., additional, Bruheim, K., additional, Rai, B., additional, Huang, F., additional, Van Der Steen-Basanik, E., additional, Cooper, R., additional, Van Limbergen, E., additional, Sundset, M., additional, Pötter, R., additional, and Kirchheiner, K., additional

Published
2020
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31. OC-0680: Risk factors for urinary incontinence in locally advanced cervix cancer: an EMBRACE analysis

Author

Spampinato, S., primary, Fokdal, L.U., additional, Pötter, R., additional, Haie-Meder, C., additional, Lindegaard, J.C., additional, Schmid, M., additional, Sturdza, A., additional, Jürgenliemk-Schulz, I., additional, Mahantshetty, U., additional, Segedin, B., additional, Hoskin, P., additional, Bruheim, K., additional, Rai, B., additional, Huang, F., additional, Cooper, R., additional, Van der Steen-Banasik, E., additional, Van Limbergen, E., additional, Nout, R., additional, Kirisits, C., additional, Kirchheiner, K., additional, and Tanderup, K., additional

Published
2020
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34. Tetraamines as lead compounds for the design of neurotransmitter receptor ligands:Focus on α-adrenergic and muscarinic receptors recognition

Author

Melchiorre, C., primary, Angeli, P., additional, Bolognesi, M.L., additional, Budriesi, R., additional, Cacciaguerra, S., additional, Chiarini, A., additional, Crucianelli, M., additional, Giardina, D., additional, Gulini, U., additional, Marucci, G., additional, Minarini, A., additional, Spampinato, S., additional, and Tumiatti, V., additional

Published
1996
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35. OC-0507 Risk factors for bladder fistula, bleeding and cystitis in cervix cancer: an EMBRACE analysis

Author

Spampinato, S., primary, Fokdal, L.U., additional, Pötter, R., additional, Haie-Meder, C., additional, Lindegaard, J.C., additional, Schmid, M., additional, Jürgenliemk-Schulz, I., additional, Mahantshetty, U., additional, Segedin, B., additional, Bruheim, K., additional, Hoskin, P., additional, Rai, B., additional, Huang, F., additional, Cooper, R., additional, Van der Steen-Banasik, E., additional, Van Limbergen, E., additional, Kirchheiner, K., additional, Kirisits, C., additional, and Tanderup, K., additional

Published
2019
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