No abstract

Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-β1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases. This review contains current research in which PFD has been used as the treatment of several diseases, and focus mainly in the outcomes related to improve inflammation and fibrogenesis. Therefore, the main goal of this review is to focus on the novel findings of PFD efficacy rather than deepen in the chemical aspects of the molecule.

IntroductionLocalized scleroderma is an inflammatory disease in its first stages and a fibrotic process in later stages, principally mediated by the transforming growth factor β. To date, there is no standard treatment. The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma.MethodsThis was an open phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times daily for 6 months. Patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well with a durometer and histologically using hematoxylin and eosin stain and Masson’s trichrome stain.ResultsThe baseline mLoSSI average scores were 5.83 ± 4.80 vs. 0.83 ± 1.75 (P = 0.002) at 6 months. The initial durometer induration of the scleroderma plaques was 35.79 ± 9.10 vs. 32.47 ± 8.97 at 6 months (P = 0.05). We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis and annex atrophy from 12.25 ± 3.25 to 9.75 ± 4.35 (P = 0.032). The 8% pirfenidone gel application was well tolerated, and no side effects were detected.ConclusionsThis is the first study on the therapeutic use of pirfenidone gel in localized scleroderma. It acts on both the inflammatory and the fibrotic phases. Considering its effectiveness, good safety profile and the advantage of topical application, pirfenidone is a treatment option in this condition.

The incidence of anterior cruciate ligament (ACL) injuries is rising every year. The autologous hamstring tendon graft, using semitendinosus tendon (SMT) and gracilis tendon (GR), is a common repair technique in the management of ACL injuries due to its multiple advantages. Using a final graft with a minimum diameter of 8 mm is necessary to avoid graft failure. The aim of this study was to find a correlation between preoperative ultrasound (USG) measurement of the SMT and GR tendon diameters (SMTd and GRd) and their actual diameters measured during the grafting procedure. In the present study, 33 male patients aged between 16 and 43 years with ACL injury that required grafting were enrolled. Before the grafting procedure, we sonographically measured the SMTd, GRd, and calculated the hamstring tendon diameter (SMTd + GRd) as the sum of these two. During surgery, we obtained the SMTd, GRd, and SMTd + GRd; we also obtained the length of both tendons and the final graft diameter (FGd). We then compared the obtained values. Mean age was 25.6 ± 7.9 years in our study population. The mean SMTd, GRd, and SMTd + GRd obtained by USG versus transoperatively were 4.9 versus 4.7 mm, 4.3 versus 3.8 mm, and 9.3 versus 8.6 mm, respectively. The mean of FGd was 8.4 mm and the mean length of both tendons was 14.2 cm. The GRd obtained by USG positively correlated with SMTd, SMT tendon length, GRd, and SMTd + GRd ( = 0.460, 0.404, 0.411, and 0.508, respectively). USG-obtained GRd predicts a final tendon diameter < 8 mm (high risk of failure) with a sensitivity, specificity, positive predictive value, and negative predictive value of 100, 54, 28 and 100%, respectively, using 4.5 mm as cutoff. Of all obtained grafts, 85% were deemed adequate (≥ 8 mm) using transoperative measurement, while 91% were ≥ 8 mm using USG measurement. The USG measurement of hamstring tendons is a useful method to predict their transoperative diameter. GRd obtained by USG is the best predictor of transoperative GRd and SMTd + GRd.