Myofibroblasts reside in the middle dermis of the keloids but do not predict the response to injection therapies: a double-blinded, randomized, controlled trial.

Introduction: Keloids form as a pathological response to skin wound healing, and their etiopathology is poorly understood. Myofibroblasts, which are cells transformed from normal fibroblasts, are believed to contribute to pathological scar formation in wounds. Methods: We carried out a double-blinded randomized controlled trial (RCT) comparing the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in treating keloids. A total of 43 patients with 50 keloids were treated with either intralesional TAC or 5-FU injections, and their clinical response was evaluated. Biopsies were collected before, during, and after injection therapy from the active border of a keloid. To understand the role of myofibroblasts in keloids, we conducted an immunohistochemical analysis to identify myofibroblasts [α-smooth muscle actin (αSMA)] from the biopsies. We first defined the three histologically distinct regions-superficial, middle, and deep dermis-in each keloid. Results: We then demonstrated that myofibroblasts almost exclusively exist in the middle dermis of the keloids as 80% of the cells in the middle dermis were αSMA positive. However, both the percentage of myofibroblasts as well as the area covered by them was substantially lower in the superficial and deep dermis than in the middle dermis of the keloids. Myofibroblasts do not predict the clinical response to intralesional injection therapies. There is no difference in the myofibroblast numbers in keloids or in the induced change in myofibroblasts between the responders and non-responders after treatment. Discussion: This study demonstrates that myofibroblasts reside almost exclusively in the middle dermis layer of the keloids, but their numbers do not predict the clinical response to intralesional injection therapies in the RCT.

Evidence for the in vivo existence and mobilisation of myeloid angiogenic cells and pericyte-like cells in wound patients after skin grafting.

Myeloid angiogenic cells (MACs) and pericyte-like cells, derived from peripheral blood mononuclear cells (MNCs) by in vitro culturing, are suggested as relevant cell types for angiogenesis and tissue repair. However, the in vivo existence and relevance of these cells has so far remained unknown. Our aim was thus to study, if MACs and pericyte-like cells exist in circulation during the wound healing of skin graft patients, and to evaluate the cellular features of wound repair. MNCs were isolated from blood samples of healthy controls (n = 4) and patients with a traumatic full thickness skin defect (n = 4) before skin grafting and on postoperative days 1 and 6. The numbers of circulating CD14+ CD45+ CD31+ CD34- MACs and CD14+ CD45+ NG2+ pericyte-like cells were assessed by flow cytometry, and gene expression of various pro-angiogenic factors was analysed by qPCR. Wound bed biopsies were taken on postoperative days 6 and 14, and MAC (CD31, CD14 and CD45) and pericyte-related markers (NG2 and PDGFRß) were histologically studied. MACs and pericyte-like cells were detected in both healthy controls and in patients. Before reconstruction, on average 18% of all circulating MNCs represented MACs and 2% pericyte-like cells in wound patients. Number of MACs significantly increased 1.1-1.7-fold in all patients 1 day after skin grafting (p < 0.01). In addition, histological analysis demonstrated effective vascularization of skin grafts, as well as presence of pericytes, and CD14 and CD45 expressing myeloid cells during wound healing. In conclusion, our data shows, for the first time, the presence and mobilisation of MACs and pericyte-like cells in human circulation.

Translation and psychometric validation of the Finnish version of the Patient Scar Assessment Scale for use in patients with burn scars.

BACKGROUND: The aim of this study was to create a Finnish scar assessment scale by translating and evaluating the psychometric properties of the Patient Scar Assessment Scale (PSAS), a part of the Patient and Observer Scar Assessment Scale (POSAS), with burn patients to enable its use in burn care. METHODS: The translation process followed international guidelines with forward and backward translations and cognitive debriefing with patients. Psychometric validation was performed with adult patients with burns who had been treated at the Helsinki Burn Centre between 2006 and 2017 with skin grafting following the excision of deep second- or third-degree burns. To ensure reproducibility, the PSAS was sent to the study participants twice. The correlation between the PSAS and health-related quality of life (HRQL) was also tested. RESULTS: In total, 192 patients, of whom 71 % were male, participated in this study. The mean (SD) age of the participants was 57 (17) years. The internal consistency of the PSAS was good, Cronbach's α 0.89 (95 % CI: 0.86-0.91). The reproducibility was also good concerning all items and the total score, ICC from 0.77 to 0.89. As expected, the total PSAS score correlated negatively with HRQL. CONCLUSION: The PSAS was successfully translated and culturally adapted into Finnish and the newly translated version has good validity and reproducibility for assessing mature burn scars.

Primary flap reconstruction of tissue defects after sarcoma surgery enables curative treatment with acceptable functional results: a 7-year review.

BACKGROUND: Sarcomas, a heterogeneous group of tumors, are challenging to treat and require multidisciplinary cooperation and planning. We analyzed the efficacy of flap reconstruction in patients with bone and soft tissue sarcoma. METHODS: Patient charts and operative records were retrospectively reviewed from January 2006 through October 2013 to identify sarcoma patient characteristics, postoperative complications, revisions, recurrences, and survival. Pedicled and/or free flap reconstruction was performed in 109 patients. Flap selection was based on defect size, and exposure of anatomically critical structures or major orthopedic implants. RESULTS: Of 109 patients, 71 (65.1 %) were men, and mean age was 56.4 years. Tumors most frequently located in a lower extremity (38.7 %). Primary sarcomas comprised 79.2 % and recurrences occurred in 18.9 %. Wide resection was performed for 65.7 %, and there were 10 planned amputations combined with flap reconstruction. A total of 111 tumors received 128 flaps: 76 pedicled flaps, 42 free flaps, and 5 combined (10 total) pedicled + free-flaps. The success rate was 94 % for the pedicled flap group, 97 % for the free-flap group, and 100 % for the pedicle + free-flap group. Of 35 patients, 5 developed deep prosthetic infections. Only one amputation due to disease progression was performed. Satisfactory functional outcome was achieved in 69 %. Survival rate during a mean (standard deviation) 3(2) year follow-up was 83.5 %. CONCLUSIONS: Primary flap reconstruction after sarcoma surgery satisfies oncologic goals. Large tumors in difficult areas can be removed and complete tumor resection achieved. Our findings indicate a high survival rate after sarcoma surgery utilizing flap reconstruction and a low recurrence rate.