P144 a Transforming Growth Factor Beta Inhibitor Peptide, Generates Antifibrogenic Effects in a Radiotherapy Induced Fibrosis Model.

Radiation-induced fibrosis (RIF) is a severe side effect related with soft tissues sarcomas (STS) radiotherapy. RIF is a multicellular process initiated primarily by TGF-ß1 that is increased in irradiated tissue, whose signaling leads to intracellular Smad2/3 phosphorylation and further induction of profibrotic target genes. P144 (Disetertide©) is a peptide inhibitor of TGF-ß1 and is proposed as a candidate compound for reducing RIF associated wound healing problems and muscle fibrosis in STS. METHODS: A treatment and control group of WNZ rabbits were employed to implement a brachytherapy animal model, through catheter implantation at the lower limb. Two days after implantation, animals received 20 Gy isodosis, intended to induce a high RIF grade. The treatment group received intravenous P144 administration following a brachytherapy session, repeated at 24-72 h post-radiation, while the control group received placebo. Four weeks later, affected muscular tissues underwent histological processing for collagen quantification and P-Smad2/3 immunohistochemistry through image analysis. RESULTS: High isodosis Brachytherapy produced remarkable fibrosis in this experimental model. Results showed retained macro and microscopical morphology of muscle in the P144 treated group, with reduced extracellular matrix fibrosis, with a lower area of collagen deposition measured through Masson's trichrome staining. Intravenous P144 also induced a significant reduction in Smad2/3 phosphorylation levels compared with the placebo group. CONCLUSIONS: P144 administration clearly reduces RIF and opens a new potential co-treatment approach to reduce complications in soft tissue sarcoma (STS) radiotherapy. Further studies are required to establish whether the dosage and timing optimization of P144 administration, in different RIF phases, might entirely avoid fibrosis associated with STS brachytherapy.

Efficacy of pedobarographic analysis to evaluate proximal medial gastrocnemius recession in patients with gastrocnemius tightness and metatarsalgia.

PURPOSE: Proximal medial gastrocnemius recession (PMGR) is a surgical procedure performed in patients with gastrocnemius tightness (GT). The purpose of this study is to evaluate the efficacy of pedobarographic analysis on PMGR in patients with GT and metatarsalgia. METHODS: This prospective study included 52 patients diagnosed with GT treated surgically with PMGR and 49 non-operated upon patients (control group). A total of 55 PMGRs (three bilateral) were performed as an isolated or combined procedure in the treatment group. Passive ankle dorsiflexion with knee flexion and extension was evaluated in all patients. In addition, pedobarographic analysis was performed before and after surgery. RESULTS: Median preoperative ankle dorsiflexion was -10.0° (equinus) with extended knee and 10.0° with flexed knee and postoperative differences in median ankle dorsiflexion was 12.5° (extended knee) (p = 0.000) and 5.0° (flexed knee) (p = 0.002). After the PMGR, the median area of the contact surface (-3.0 cm2) (p = 0.009), the maximum (-13,239.0 Pa) (p = 0.019) and mean pressure (-2,942.0 Pa) and the forefoot force (-70.0 N) (p = 0.000) decreased. An increase in hindfoot force (20.0 N), hindfoot bearing time (4.0 ms) (p = 0.005), and forefoot bearing time (1.0 ms) was also observed. CONCLUSIONS: Pedobarographic analysis is an efficient tool to evaluate surgical procedures that assess metatarsal overload. PMGR is an effective surgical procedure to improve passive ankle range of motion and decrease forefoot plantar overload.