{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:19:37Z","timestamp":1760149177044,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Klippel\u2013Trenanauy syndrome (KTS) is a rare genetic disease determined by overexpression of the phosphatidylinositol-4-5-bisphosphate 3 kinase catalytic subunit (PIK3CA) gene. The clinical presentation is characterized by venous and capillary malformations and lymphatic malformation. To date, no definitive treatment has been suggested in order to improve the clinical symptoms related to the developments of a skin wound. In this case, we describe a young man with KTS that developed a severe skin wound in the lower right limb unresponsive to the common treatment but responsive to a treatment with oxygen-ozone therapy, pulsed magnetic fields (diamagnetic treatment), and topical fixed association of cocum caprylate, oleic acid, quercetin, and 18-\u03b2 glycyrrhetinic acid. This is the first case that supports a multistep approach to treat a rare and severe disease, and we hope that other studies can support our data.<\/jats:p>","DOI":"10.3390\/reports6030033","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T04:27:13Z","timestamp":1689827233000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multiple Synergic Treatment for Non-Healing Ulcer Management in a Patient with Klippel\u2013Trenaunay Syndrome"],"prefix":"10.3390","volume":"6","author":[{"given":"Cristina","family":"Vocca","sequence":"first","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianmarco","family":"Marcian\u00f2","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9938-5259","authenticated-orcid":false,"given":"Vincenzo","family":"Rania","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Catarisano","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Palleria","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Ciranni","sequence":"additional","affiliation":[{"name":"Vascular Surgery Unit, Department of Medical and Surgical Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Torcia","sequence":"additional","affiliation":[{"name":"Vascular Surgery Unit, Department of Medical and Surgical Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-7412","authenticated-orcid":false,"given":"Raffaele","family":"Serra","sequence":"additional","affiliation":[{"name":"Vascular Surgery Unit, Department of Medical and Surgical Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Monea","sequence":"additional","affiliation":[{"name":"Research Center FAS@UMG, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1906-5109","authenticated-orcid":false,"given":"Giuseppe","family":"Spaziano","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-6579","authenticated-orcid":false,"given":"Giovambattista","family":"De Sarro","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"},{"name":"Research Center FAS@UMG, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6746-6751","authenticated-orcid":false,"given":"Rita","family":"Citraro","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"},{"name":"Research Center FAS@UMG, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-7902","authenticated-orcid":false,"given":"Luca","family":"Gallelli","sequence":"additional","affiliation":[{"name":"Operative Unit of Pharmacology and Pharmacovigilance, \u201cRenato Dulbecco University Hospital\u201d, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"},{"name":"Research Center FAS@UMG, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy"},{"name":"Medifarmagen Srl, Spin Off\u2014University of Catanzaro and Mater Domini Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","unstructured":"Naganathan, S., and Tadi, P. (2023, February 25). Klippel Trenaunay Weber Syndrome, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK558989\/?report=printable."},{"key":"ref_2","first-page":"3","article-title":"A Rare Case of Klippel-Tr\u00e9naunay Syndrome","volume":"14","author":"Arasu","year":"2022","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1067\/j.cpradiol.2017.10.003","article-title":"International Society for the Study of Vascular Anomalies (ISSVA) classification for vascular anomalies","volume":"48","author":"Darrow","year":"2019","journal-title":"Curr. Probl. Diagn. Radiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/exd.12826","article-title":"Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS)","volume":"25","author":"Vahidnezhad","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100634","DOI":"10.1016\/j.tvir.2019.100634","article-title":"Klippel-Trenaunay Syndrome","volume":"22","author":"John","year":"2019","journal-title":"Tech. Vasc. Interv. Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1097\/RCT.0000000000000895","article-title":"Imaging findings of Klippel-Trenaunay syndrome","volume":"43","year":"2019","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_7","first-page":"231","article-title":"Angioma formation in connection with hypertrophy of limbs and hemihypertrophy","volume":"19","year":"1907","journal-title":"Br. J. Derm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1177\/0268355516664212","article-title":"Parkes Weber syndrome\u2014Diagnostic and management paradigms: A systematic review","volume":"32","author":"Banzic","year":"2017","journal-title":"Phlebology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1590\/1677-5449.005417","article-title":"Klippel-Trenaunay and Parkes-Weber syndromes: Two case reports","volume":"16","author":"Chagas","year":"2017","journal-title":"J. Vasc. Bras."},{"key":"ref_10","first-page":"159","article-title":"Chronic Wounds: Evaluation and Management","volume":"101","author":"Bowers","year":"2020","journal-title":"Am. Fam. Physician"},{"key":"ref_11","first-page":"298","article-title":"Venous Ulcers: Diagnosis and Treatment","volume":"100","author":"Gan","year":"2019","journal-title":"Am. Fam. Physician"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3390\/nursrep12030067","article-title":"Wound Care Self-Efficacy Assessment of Italian Registered Nurses and Wound Care Education in Italian Nursing Education System: A Cross-Sectional Study","volume":"12","author":"Ielapi","year":"2022","journal-title":"Nurs. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Roberti, R., Marcian\u00f2, G., Casarella, A., Rania, V., Palleria, C., Muraca, L., Citraro, R., De Sarro, G., Serra, R., and Romeo, P. (2022). High-Intensity, Low-Frequency Pulsed Electromagnetic Field as an Odd Treatment in a Patient with Mixed Foot Ulcer: A Case Report. Reports, 5.","DOI":"10.3390\/reports5010003"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pullano, S.A., Marcian\u00f2, G., Bianco, M.G., Oliva, G., Rania, V., Vocca, C., Cione, E., De Sarro, G., Gallelli, L., and Romeo, P. (2022). FT-IR Analysis of Structural Changes in Ketoprofen Lysine Salt and KiOil Caused by a Pulsed Magnetic Field. Bioengineering, 9.","DOI":"10.3390\/bioengineering9100503"},{"key":"ref_15","unstructured":"PERISO (2022, May 24). Diamagnetic Therapy\u2014PERISO. Available online: https:\/\/periso.ch\/wp-content\/uploads\/2021\/11\/CTU-MGA-20-ita.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rania, V., Marcian\u00f2, G., Casarella, A., Vocca, C., Palleria, C., Calabria, E., Spaziano, G., Citraro, R., De Sarro, G., and Monea, F. (2023). Oxygen\u2014Ozone Therapy in Cervicobrachial Pain: A Real-Life Experience. J. Clin. Med., 12.","DOI":"10.3390\/jcm12010248"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s10103-008-0564-0","article-title":"Influence of different types of electromagnetic fields on skin reparatory processes in experimental animals","volume":"24","author":"Matic","year":"2009","journal-title":"Lasers Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8429","DOI":"10.1002\/slct.201902572","article-title":"Quercetin-3-Oleate Contributes to Skin Wound Healing Targeting FFA1 \/GPR40","volume":"4","author":"Carullo","year":"2019","journal-title":"ChemistrySelect"},{"key":"ref_19","first-page":"469","article-title":"Klippel-Trenaunay syndrome: The risks and benefits of vascular interventions","volume":"110","author":"Gloviczki","year":"1991","journal-title":"Surgery"},{"key":"ref_20","first-page":"9","article-title":"Venous disorders: Treatment with sclerosant foam","volume":"47","author":"Bergan","year":"2006","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0025-6196(11)63615-X","article-title":"Klippel-Tr\u00e9naunay syndrome: Spectrum and management","volume":"73","author":"Jacob","year":"1998","journal-title":"Mayo Clin. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pasek, J., Szajkowski, S., Travagli, V., and Cie\u015blar, G. (2023). Topical Hyperbaric Oxygen Therapy Versus Local Ozone Therapy in Healing of Venous Leg Ulcers. Int. J. Environ. Res. Public. Health, 20.","DOI":"10.3390\/ijerph20031967"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1089\/dia.2011.0018","article-title":"Efficacy of ozone-oxygen therapy for the treatment of diabetic foot ulcers","volume":"13","author":"Wainstein","year":"2011","journal-title":"Diabetes Technol. Ther."},{"key":"ref_24","first-page":"CD008474","article-title":"Ozone therapy for treating foot ulcers in people with diabetes","volume":"2015","author":"Liu","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/iwj.12907","article-title":"Ozone therapy for the treatment of chronic wounds: A systematic review","volume":"15","author":"Fitzpatrick","year":"2018","journal-title":"Int. Wound J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2740963","DOI":"10.1155\/2017\/2740963","article-title":"Adenosine Receptors as a Biological Pathway for the Anti-Inflammatory and Beneficial Effects of Low Frequency Low Energy Pulsed Electromagnetic Fields","volume":"2017","author":"Varani","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_27","first-page":"59","article-title":"Effect of pulsed electromagnetic field treatment on programmed resolution of inflammation pathway markers in human cells in culture","volume":"8","author":"Kubat","year":"2015","journal-title":"J. Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.spinee.2016.01.003","article-title":"Pulsed electromagnetic field (PEMF) treatment reduces expression of genes associated with disc degeneration in human intervertebral disc cells","volume":"16","author":"Miller","year":"2016","journal-title":"Spine J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/bem.10078","article-title":"Pulsed Electromagnetic Fields Prevent Osteoporosis in an Ovariectomized Female Rat Model: A Prostaglandin E2-Associated Process","volume":"24","author":"Chang","year":"2003","journal-title":"Bioelectromagnetics"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Premi, E., Benussi, A., La Gatta, A., Visconti, S., Costa, A., Gilberti, N., Cantoni, V., Padovani, A., Borroni, B., and Magoni, M. (2018). Modulation of long-term potentiation-like cortical plasticity in the healthy brain with low frequency-pulsed electromagnetic fields. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0434-z"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/bem.22330","article-title":"The Effect of Pulsed Electromagnetic Fields on Angiogenesis","volume":"42","author":"Peng","year":"2021","journal-title":"Bioelectromagnetics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/bem.21917","article-title":"Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism","volume":"36","author":"Ahmed","year":"2015","journal-title":"Bioelectromagnetics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/bem.22343","article-title":"A Low-Frequency Pulsed Magnetic Field Reduces Neuropathic Pain by Regulating NaV1.8 and NaV1.9 Sodium Channels at the Transcriptional Level in Diabetic Rats","volume":"42","author":"Coskun","year":"2021","journal-title":"Bioelectromagnetics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1016\/j.jmmm.2012.02.073","article-title":"Effect of pulse magnetic field stimulation on calcium channel current","volume":"324","author":"Fan","year":"2012","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1007\/s12010-016-2289-z","article-title":"Neuroprotective Effect of Low Frequency-Pulsed Electromagnetic Fields in Ischemic Stroke","volume":"181","author":"Urnukhsaikhan","year":"2017","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12982","DOI":"10.1111\/cpr.12982","article-title":"Magnetic fields as a potential therapy for diabetic wounds based on animal experiments and clinical trials","volume":"54","author":"Lv","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/jor.1100080217","article-title":"Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: A double-blind study","volume":"8","author":"Ieran","year":"1990","journal-title":"J. Orthop. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1365-2133.1992.tb08047.x","article-title":"A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: A double-blind, placebo-controlled clinical trial","volume":"127","author":"Stiller","year":"1992","journal-title":"Br. J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/01.ASW.0000462012.58911.53","article-title":"Pulsed Electromagnetic Field Therapy Promotes Healing and Microcirculation of Chronic Diabetic Foot Ulcers: A Pilot Study","volume":"28","author":"Kwan","year":"2015","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/jid.2011.265","article-title":"Oral administration of oleic or linoleic acid accelerates the inflammatory phase of wound healing","volume":"132","author":"Rodrigues","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/iwj.13299","article-title":"Nano-hydrogel embedded with quercetin and oleic acid as a new formulation in the treatment of diabetic foot ulcer: A pilot study","volume":"17","author":"Gallelli","year":"2020","journal-title":"Int. Wound J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/ics.12548","article-title":"18b-Glycyrrhetinic acid: Its core biological properties and dermatological applications","volume":"41","author":"Kowalska","year":"2019","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hung, C.-F., Hsiao, C.-Y., Hsieh, W.-H., Li, H.-J., Tsai, Y.-J., Lin, C.-N., Chang, H.-H., and Wu, N.-L. (2017). 18-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182981"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46616","DOI":"10.1074\/jbc.M209003200","article-title":"Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery","volume":"277","author":"Hara","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/6\/3\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:15:17Z","timestamp":1760127317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/6\/3\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,20]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["reports6030033"],"URL":"https:\/\/doi.org\/10.3390\/reports6030033","relation":{},"ISSN":["2571-841X"],"issn-type":[{"type":"electronic","value":"2571-841X"}],"subject":[],"published":{"date-parts":[[2023,7,20]]}}}