{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:23:13Z","timestamp":1787746993430,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Fluoroquinolones cause Achilles tendinopathy within a narrow, early therapeutic window, yet preventive strategies given alongside these antibiotics remain largely untested. This exploratory pilot study assessed whether four mechanistically distinct adjuvants attenuated histopathological tendon change in a rabbit model of levofloxacin exposure. Methods: Twenty-one male New Zealand White rabbits received oral levofloxacin (100 \u00b5g\/kg\/day, seven days). A contralateral-limb design yielded 42 tendons (two cohorts provided paired limb-specific comparisons and a third cohort received the systemic intervention). Animals were allocated to various groups, receiving platelet-rich plasma (PRP), injectable porcine collagen, oral vitamin E + selenium, topical essential oils with augmented soft-tissue mobilization (ASTM), or a levofloxacin-only control. The main outcome was a modified Bonar composite (tenocyte morphology, cellularity, vascularity, paratendinous fibrosis; 0\u201312) at three months; additional outcomes were the individual domains and ultrasonographic tendon thickness. Results: Composite scores were low throughout (group medians 2.0\u20134.0) and did not differ between groups (H = 3.663, p = 0.45); no domain differed, and the untreated control did not show the greatest change. Within animals, collagen-treated tendons scored higher than the paired essential-oil tendons (median difference +3.0, nominal p = 0.031, Bonferroni-adjusted p = 0.062). Tendon thickness increased by day 14 only with vitamin E + selenium (+14.1%; p = 0.003, and p = 0.006 adjusted for baseline); this finding arose in a separate cohort with thinner baseline tendons, cannot be confidently attributed to the intervention, and was unrelated to histopathology (\u03c1 = \u22120.02, p = 0.91). Macroscopic findings differed between groups (nominal p = 0.031) without predicting tissue grade. Conclusions: No statistically detectable difference in the study-specific four-domain composite was identified among the treatment conditions; the study lacked a levofloxacin-free control and could not provide a definitive efficacy assessment. The model produced only mild pathology, limiting its power, and neither imaging nor gross inspection predicted tissue-level change. These preliminary observations are hypothesis-generating and are intended to inform the design of an adequately powered confirmatory study. The findings are inconclusive for efficacy; the design cannot distinguish lack of adjuvant efficacy from failure of the model to induce measurable disease.<\/jats:p>","DOI":"10.3390\/jcm15176596","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:53:42Z","timestamp":1787745222000},"page":"6596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant Interventions in Levofloxacin-Exposed Rabbit Achilles Tendons: An Exploratory Controlled Pilot Study with Histopathological and Ultrasonographic Endpoints"],"prefix":"10.3390","volume":"15","author":[{"given":"Oana-Maria","family":"Mi\u0219c\u0103","sequence":"first","affiliation":[{"name":"Doctoral School Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liviu-Coriolan","family":"Mi\u0219c\u0103","sequence":"additional","affiliation":[{"name":"Aspire Orthopaedics, UPMC Sports Surgery Clinic, Northwood Avenue, Santry Demesne, D09 C523 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5219-5466","authenticated-orcid":false,"given":"Andreea-Adriana","family":"Neam\u021bu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Pathology, Clinical County Emergency Hospital of Arad, Andrenyi Karoly Str. No. 2\u20134, 310037 Arad, Romania"},{"name":"Department of Pathology, \u201cPius Br\u00eenzeu\u201d Clinical County Emergency Hospital Timi\u0219oara, Liviu Rebreanu Boulevard No. 156, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-8271","authenticated-orcid":false,"given":"Laura","family":"Maghiar","sequence":"additional","affiliation":[{"name":"Department of Psycho-Neurosciences and Rehabilitation, Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Str. No. 1, 410087 Oradea, Romania"},{"name":"Department of Dermatovenerology, Clinical County Emergency Hospital Bihor, Gheorghe Doja Str. No. 65, 410169 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Constantin","family":"Croicu","sequence":"additional","affiliation":[{"name":"Veterinaria\u2014Veterinary Orthopedics and Traumatology Center Timi\u0219oara, Constantin Br\u00e2ncoveanu Blvd., No. 125a, 300502 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Baderca","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, 300041 Timi\u0219oara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Service of Pathology, Emergency City Hospital, 300254 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0067-8247","authenticated-orcid":false,"given":"Amalia Raluca","family":"Ceau\u0219u","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, 300041 Timi\u0219oara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Cristina","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Doctoral School Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1552-7961","authenticated-orcid":false,"given":"Valentin-Cristian","family":"Iovin","sequence":"additional","affiliation":[{"name":"Doctoral School Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-6872","authenticated-orcid":false,"given":"Titus","family":"Grecu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Cristina","family":"Grecu","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Department\u2013Casa Austria, \u201cPius Br\u00eenzeu\u201d Clinical County Emergency Hospital Timi\u0219oara, Liviu Rebreanu Boulevard No. 156, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra-Magdalena","family":"Ioana","sequence":"additional","affiliation":[{"name":"Doctoral School Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Anatomy and Embryology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-7485","authenticated-orcid":false,"given":"Petri\u0219or Zorin","family":"Cr\u0103iniceanu","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Department\u2013Casa Austria, \u201cPius Br\u00eenzeu\u201d Clinical County Emergency Hospital Timi\u0219oara, Liviu Rebreanu Boulevard No. 156, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-7677","authenticated-orcid":false,"given":"Andrei Gheorghe Marius","family":"Motoc","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41572-025-00602-9","article-title":"Achilles tendinopathy","volume":"11","author":"Traweger","year":"2025","journal-title":"Nat. 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