Therapeutic administration of mouse mast cell protease 6 improves functional recovery after traumatic spinal cord injury in mice by promoting remyelination and reducing glial scar formation.

Traumatic spinal cord injury (SCI) most often leads to permanent paralysis due to the inability of axons to regenerate in the adult mammalian central nervous system (CNS). In the past, we have shown that mast cells (MCs) improve the functional outcome after SCI by suppressing scar tissue formation at the lesion site via mouse mast cell protease 6 (mMCP6). In this study, we investigated whether recombinant mMCP6 can be used therapeutically to improve the functional outcome after SCI. Therefore, we applied mMCP6 locally via an intrathecal catheter in the subacute phase after a spinal cord hemisection injury in mice. Our findings showed that hind limb motor function was significantly improved in mice that received recombinant mMCP6 compared with the vehicle-treated group. In contrast to our previous findings in mMCP6 knockout mice, the lesion size and expression levels of the scar components fibronectin, laminin, and axon-growth-inhibitory chondroitin sulfate proteoglycans were not affected by the treatment with recombinant mMCP6. Surprisingly, no difference in infiltration of CD4+ T cells and reactivity of Iba-1+ microglia/macrophages at the lesion site was observed between the mMCP6-treated mice and control mice. Additionally, local protein levels of the pro- and anti-inflammatory mediators IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-α, IFNγ, and MCP-1 were comparable between the two treatment groups, indicating that locally applied mMCP6 did not affect inflammatory processes after injury. However, the increase in locomotor performance in mMCP6-treated mice was accompanied by reduced demyelination and astrogliosis in the perilesional area after SCI. Consistently, we found that TNF-α/IL-1ß-astrocyte activation was decreased and that oligodendrocyte precursor cell (OPC) differentiation was increased after recombinant mMCP6 treatment in vitro. Mechanistically, this suggests effects of mMCP6 on reducing astrogliosis and improving (re)myelination in the spinal cord after injury. In conclusion, these data show for the first time that recombinant mMCP6 is therapeutically active in enhancing recovery after SCI.

Single-layer vs double-layer uterine closure during cesarean delivery: 3-year follow-up of a randomized controlled trial (2Close study).

BACKGROUND: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. OBJECTIVE: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. STUDY DESIGN: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). RESULTS: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. CONCLUSION: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.

Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

Aesthetic outcome of intermediate closure versus intermediate closure followed by 2-octyl cyanoacrylate: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Dermatologic surgeons are increasingly using surgical adhesives in their practice. Studies comparing sutured wounds to those that utilize a combination of suturing and skin adhesive have not been previously conducted. OBJECTIVE: To compare the cosmetic outcome and patient wound care satisfaction of an intermediate suture closure with an intermediate suture closure followed by the application of 2-octyl cyanoacrylate (2-OCA). METHODS: Fifty patients were enrolled in a randomized, evaluator-blinded, split-scar study. Following intermediate sutured closure of a surgical defect, one side of the wound was randomized to receive an additional application of 2-OCA. After 3 months, the scar was assessed using the POSAS tool and patients reported wound care preferences. RESULTS: As the primary outcome measure, the mean sum of observer POSAS was 12.80 for sutured closure alone versus 12.40 for sutured closures followed by 2-OCA (P = .49). LIMITATIONS: Single-center study of a relatively homogenous population. CONCLUSION: Although there were no significant differences in scar cosmesis, both patients and observers tended to prefer the side with an additional application of 2-OCA in most POSAS components, in overall opinion, and in patient wound care satisfaction. Dermatologic surgeons may add this to their practice without sacrificing scar outcomes or patient satisfaction.

Aesthetic outcome of running subcuticular suture versus running horizontal mattress suture in closure of linear wounds of the trunk and extremities: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Both running horizontal mattress (HM) and running subcuticular (SQ) suturing techniques have been suggested to be superior to other running cuticular suturing techniques. These 2 techniques have not been directly compared. OBJECTIVE: To compare cosmetic outcomes between a running HM and a running SQ technique in a split scar model following linear closure of trunk and extremity defects. METHODS: Fifty patients were enrolled in a randomized, evaluator-blinded, split-scar study. One side of the surgical wound was randomized to receive one intervention (HM vs SQ) with the other side receiving the alternate intervention. The primary outcome was the Patient and Observer Scar Assessment Scale (POSAS) score at a minimum of 3 months postoperatively. RESULTS: Observer POSAS sum of components was 19.49 and 17.76 for HM and SQ, respectively (P = .14). The mean score for patient overall opinion was 4.71 for HM and 3.50 for the SQ technique (P = .02). Overall opinion scores of evaluators were 3.87 and 3.29 for HM and SQ, respectively (P = .03). LIMITATIONS: Single-center study of a relatively homogenous population. CONCLUSION: Although there was no significant difference in the sum of POSAS components between HM and SQ (P = .14), both patients and evaluators had a superior overall opinion of the SQ-treated side (patient P = .02, evaluator P = .03).

Early postoperative water exposure does not increase complications in cutaneous surgeries: A randomized, investigator-blinded, controlled trial.

BACKGROUND: Patients are often advised to keep the initial postoperative dressings dry and undisturbed for 24 to 72 hours. However, these requirements may result in significant disruption of patients' activities of daily living, such as bathing, leisure, and exercise. OBJECTIVE: Compare standard management of keeping wounds dry and covered (48 hours) with early (6 hours) postoperative water exposure. METHODS: Investigator-blinded, randomized (1:1), controlled trial evaluating rate of infection and additional outcomes of interest. RESULTS: Overall, 437 patients were randomized to either the early (6-hour) water exposure (n = 218) intervention group or the standard cohort (n = 219). The incidence of culture-proven infection in the intervention group (1.8%) was similar to the standard group (1.4%) (P > .99). There was also no difference in rates of bleeding or bruising. Scar assessment using the Patient and Observer Scar Assessment Scale revealed similar scar outcomes. LIMITATIONS: Single site, academic center. CONCLUSION: Surgical wounds can be allowed to get wet in the immediate postoperative period with no increased incidence of infection or other complications and with similar cosmesis.

Effect of Laser and Energy-based Device Therapies to Minimize Surgical Scar Formation: A Systematic Review and Network Meta-analysis.

Utilization of lasers and energy-based devices for surgical scar minimization has been substantially evaluated in placebo-controlled trials. The aim of this study was to compare reported measures of efficacy of lasers and energy-based devices in clinical trials in preventing surgical scar formation in a systematic review and network meta-analyses. Five electronic databases, PubMed, Scopus, Embase, ClinicalTrials.gov, and the Cochrane Library, were searched to retrieve relevant articles. The search was limited to randomized controlled trials that reported on clinical outcomes of surgical scars with treatment initiation no later than 6 months after surgery and a follow-up period of at least 3 months. A total of 18 randomized controlled trials involving 482 participants and 671 postsurgical wounds were included in the network meta-analyses. The results showed that the most efficacious treatments were achieved using low-level laser therapy) (weighted mean difference -3.78; 95% confidence interval (95% CI) -6.32, -1.24) and pulsed dye laser (weighted mean difference -2.46; 95% CI -4.53, -0.38). Nevertheless, low-level laser therapy and pulsed dye laser demonstrated comparable outcomes in surgical scar minimization (weighted mean difference -1.32, 95% CI -3.53, 0.89). The findings of this network meta-analyses suggest that low-level laser therapy and pulsed dye laser are both effective treatments for minimization of scar formation following primary closure of surgical wounds with comparable treatment outcomes.

Pressure-garment therapy for preventing hypertrophic scarring after burn injury.

BACKGROUND: Burn damage to skin often results in scarring; however in some individuals the failure of normal wound-healing processes results in excessive scar tissue formation, termed 'hypertrophic scarring'. The most commonly used method for the prevention and treatment of hypertrophic scarring is pressure-garment therapy (PGT). PGT is considered standard care globally; however, there is continued uncertainty around its effectiveness. OBJECTIVES: To evaluate the benefits and harms of pressure-garment therapy for the prevention of hypertrophic scarring after burn injury. SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registers on 8 June 2023 with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing PGT (alone or in combination with other scar-management therapies) with scar management therapies not including PGT, or comparing different PGT pressures or different types of PGT. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion using predetermined inclusion criteria, extracted data, and assessed risk of bias using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 15 studies in this review (1179 participants), 14 of which (1057 participants) presented useable data. The sample size of included studies ranged from 17 to 159 participants. Most studies included both adults and children. Eight studies compared a pressure garment (with or without another scar management therapy) with scar management therapy alone, five studies compared the same pressure garment at a higher pressure versus a lower pressure, and two studies compared two different types of pressure garments. Studies used a variety of pressure garments (e.g. in-house manufactured or a commercial brand). Types of scar management therapies included were lanolin massage, topical silicone gel, silicone sheet/dressing, and heparin sodium ointment. Meta-analysis was not possible as there was significant clinical and methodological heterogeneity between studies. Main outcome measures were scar improvement assessed using the Vancouver Scar Scale (VSS) or the Patient and Observer Scar Assessment Scale (POSAS) (or both), pain, pruritus, quality of life, adverse events, and adherence to therapy. Studies additionally reported a further 14 outcomes, mostly individual scar parameters, some of which contributed to global scores on the VSS or POSAS. The amount of evidence for each individual outcome was limited. Most studies had a short follow-up, which may have affected results as the full effect of any therapy on scar healing may not be seen until around 18 months. PGT versus no treatment/lanolin We included five studies (378 participants). The evidence is very uncertain on whether PGT improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, adverse events, and adherence. No study used the POSAS or assessed quality of life. One additional study (122 participants) did not report useable data. PGT versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, adherence, and other scar parameters. It is possible that silicone may result in fewer adverse events or better adherence compared with PGT but this was also based on very low-certainty evidence. PGT plus silicone versus no treatment/lanolin We included two studies (200 participants). The evidence is very uncertain on whether PGT plus silicone improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, and adverse events. No study used the POSAS or assessed quality of life or adherence. PGT plus silicone versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT plus silicone compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. PGT plus scar management therapy including silicone versus scar management therapy including silicone We included one study (88 participants). The evidence is very uncertain on the effect of PGT plus scar management therapy including silicone versus scar management therapy including silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. High-pressure versus low-pressure garments We included five studies (262 participants). The evidence is very uncertain on the effect of high pressure versus low pressure PGT on adverse events and adherence. No study used the VSS or the POSAS or assessed pain, pruritus, or quality of life. Different types of PGT (Caroskin Tricot + an adhesive silicone gel sheet versus Gecko Nanoplast (silicone gel bandage)) We included one study (60 participants). The evidence is very uncertain on the effect of Caroskin Tricot versus Gecko Nanoplast on the POSAS, pain, pruritus, and adverse events. The study did not use the VSS or assess quality of life or adherence. Different types of pressure garments (Jobst versus Tubigrip) We included one study (110 participants). The evidence is very uncertain on the adherence to either Jobst or Tubigrip. This study did not report any other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend using either PGT or an alternative for preventing hypertrophic scarring after burn injury. PGT is already commonly used in practice and it is possible that continuing to do so may provide some benefit to some people. However, until more evidence becomes available, it may be appropriate to allow patient preference to guide therapy.

The W-Plasty Serial Excision Method for Treating Medium Congenital Melanocytic Nevi: A Retrospective Analytical Study.

BACKGROUND: Serial excision remains the most commonly used surgical procedure for treating congenital melanocytic nevus (CMN). It is critical to remove as much of the lesion as possible with each procedure to reduce the number of procedures and to shorten the treatment duration. OBJECTIVE: To investigate the clinical efficacy of W-plasty serial excision for the repair of postoperative CMN defects. METHODS: A retrospective analysis of patients with medium CMN was conducted from April 2018 to March 2022. Treatment options were divided into elliptical serial excision (10 cases) and W-plasty serial excision (10 cases). RESULTS: Follow-up occurred over 6 months. The number of elliptical excision procedures was 2 to 4 (mean 2.9). The scar-to-lesion length ratio was 1.5 to 2.0 (mean 1.7). The mean Vancouver Scar Scale (VSS) score was 5.40 ± 0.42. The number of W-plasty excision procedures was 2 to 3 (mean 2.2). The scar-to-lesion length ratio was 1.2 to 1.5 (mean 1.4). The mean VSS score was 2.70 ± 0.26. W-plasty excision was superior to elliptical excision regarding the number of procedures and the effect on postoperative scars. CONCLUSION: W-plasty serial excision can be considered a suitable option for the excision of medium CMN, leading to excellent results.

Using Neuromodulators to Improve Scar Formation, Keloids, Rosacea, and Antiaging.

BACKGROUND: Botulinum toxin A (BoNT-A) treatment has many uses in dermatology. Its mechanism of action and long-term effects for scar formation, rosacea, and antiaging are still being investigated. OBJECTIVE: To conduct a literature review on BoNT-A to further investigate its use in scar formation, rosacea, and antiaging. METHODS: A literature review was conducted using PubMed on botulinum toxin treatment for scar formation, rosacea, and antiaging. Studies discussing the toxin mechanism of action and treatment algorithm were included. The authors also provided their personal experience in BoNT-A use for these 3 conditions. RESULTS: The mechanism of action of Botulinum toxin A in improving scar formation, rosacea, and antiaging is now better understood. While it is effective in the short term, little is still known about how frequently treatment needs to be repeated and if there are any long-term effects. CONCLUSION: While in vitro studies have supporting evidence on the mechanism of action of BoNT-A on scar formation, rosacea, and antiaging, further studies are needed to identify long-term treatment effects.

Advances in the assessment of cosmetic outcomes, sensory alteration in surgical areas, and health-related quality of life of endoscopic thyroidectomy.

BACKGROUND: Endoscopic thyroidectomy has been preliminarily proven effective and safe for thyroid diseases. The cosmetic outcomes and life quality are critical contents of postoperative assessment. This review will primarily focus on the assessment methods and results related to cosmetic outcomes, sensory alteration of surgical area, and quality of life following endoscopic thyroidectomy. METHODS: A comprehensive search of published articles within the last decade was conducted using the terms "endoscopic/robotic thyroidectomy," "patient satisfaction scores," "questionnaire," "quality of life," and "cosmetic" in PubMed. RESULTS: Assessment methods for postoperative cosmetic satisfaction and sensory alterations encompassed verbal/visual analog scales, scar evaluations, Semmes-Weinstein monofilament tests, and more. The evaluation of postoperative quality of life in endoscopic thyroidectomy involved tools such as SF-36, SF-12, thyroid-specific questionnaires, thyroid cancer-specific quality of life questionnaires (THYCA-QOL), as well as assessments related to voice and swallow function. The cosmetic results of endoscopic thyroidectomy generally surpassed those of open thyroidectomy, while the quality of life in endoscopic procedures was either superior or equivalent to that in open thyroidectomy, especially with respect to general health, role emotion, and vitality. CONCLUSIONS: Assessments of cosmetic outcomes and sensory alterations following endoscopic thyroidectomy predominantly relied on patients' subjective feelings. The objective and subjective perspectives of scar assessments remain underutilized. In addition, postoperative laryngoscopy and voice function assessments in endoscopic thyroidectomy procedures require more attention.

Updated criteria for the approval of subsequent pregnancy after cesarean section with a transverse uterine fundal incision based on 17 years of experience.

In the case of placenta previa-accreta when the placenta covers the entire anterior uterine wall, it is difficult to avoid transecting the placenta by traditional low-transverse cesarean section (CS), resulting in catastrophic hemorrhage and fetal anemia. To prevent this critical risk, we developed the CS with transverse uterine fundal incision (TUFI) and this technique has been widely used as a beneficial surgical method in clinical practice owing to its safety advantages for the mother and neonate since our first report. However, the risk of uterine rupture during a subsequent pregnancy remains unclear. Based on our 17 years of experience, patients who require TUFI do not need to avoid this beneficial operative method simply because of their desire to conceive again, as long as certain conditions can be met. To approve a post-TUFI pregnancy, an appropriate suture method, delay in conception for at least 12 months with evaluation of the TUFI scar, and cautious postoperative management are at a minimum essential. In this article, we showed our recommendation for operative procedure and discuss the current status of the management of post-TUFI pregnancies based on the evaluation of the TUFI wound scar and experience with postoperative pregnancies.

A Systematic Review on Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, including chlorogenic acid, thymol, and eugenol from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages. This review provides mechanistic insights into the significant role of pharmacologically demonstrated natural products in wound healing processes.

Vertical Scar Reduction Mammaplasty Using the Superomedial-Based Pedicle Technique in Gigantomastia.

BACKGROUND: Breast reduction surgery has witnessed significant advancements in recent years; however, it continues to pose challenges for both surgeons and patients when dealing with cases involving excessive breast volume and severe breast ptosis. This study aimed to assess the aesthetic outcomes and the impact on the quality of life, as measured by the BREAST-Q questionnaire, in patients with gigantomastia and severe breast ptosis who underwent reduction mammaplasty using the superomedial-based pedicle technique. METHODS: We present a retrospective series comprising 84 patients who underwent reduction mammoplasty utilizing the superomedial pedicle technique. The surgical resections exceeded 1 kg per breast, with a mean resection weight of 1506.58 g (right breast) and 1500.32 g (left breast). The preoperative mean suprasternal notch to nipple distance measured 40.50 cm (right breast) and 40.38 cm (left breast). Postoperatively, the patients were followed up for a minimum of 6 months. Both preoperative and postoperative BREAST-Q surveys were administered to the participants, and scores were analyzed using descriptive statistics. RESULTS: Complications were observed in 3 patients (3.57%), characterized by partial loss of the areola, which resolved spontaneously over time. Additionally, 2 cases of hematoma and 2 instances of minor delayed wound healing were reported. All patients expressed satisfaction with their aesthetic outcomes, as they achieved a natural breast shape and minimal scarring, along with symptomatic relief. CONCLUSIONS: The superomedial pedicle reduction mammaplasty technique has demonstrated its ability to produce satisfactory aesthetic outcomes and long-term benefits in patients with excessively large breasts. Careful patient selection and postoperative management are vital for achieving optimal results. Further investigations involving larger sample sizes and longer follow-up periods are warranted to validate our findings. LEVEL OF EVIDENCE: IV.

Verapamil inhibits inflammation and promotes autophagy to alleviate ureteral scar by regulation of CaMK IIδ/STAT3 axis.

BACKGROUND: Ureteral stricture (US) is a pathological stenosis in the urinary tract characterized by increased collagen synthesis and inflammation. Autophagy activation has been shown to ameliorate tissue fibrosis and protect against fibrotic diseases. Verapamil has beneficial therapeutic benefits on fibrotic disorders. The pharmacological effects of verapamil on fibroblast autophagy in US and the underlying mechanism need to be investigated further. METHODS: US patients were recruited to isolate scar tissues, hematoxylin-eosin (HE) and Masson trichrome staining were performed to analyze histopathological changes. The US animal model was established and administered with verapamil (0.05 mg/kg) in the drinking water. Transforming growth factor (TGF)-ß1 was adopted to facilitate collagen synthesis in fibroblasts. The mRNA and protein expressions were examined by qRT-PCR, western blot, immunofluorescence and immunohistochemistry. ELISA was adopted to measure interleukin (IL)-1ß and IL-6 levels. Molecular interaction experiments like dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between signal transducers and activators of transcription 3 (STAT3) and RNA polymerase II associated factor 1 (PAF1). RESULTS: Herein, our results revealed that verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited inflammation and fibrosis by repressing Ca2+/calmodulin-dependent protein kinase II (CaMK II) δ-mediated STAT3 activation. Our following tests revealed that STAT3 activated PAF1 transcription. PAF1 upregulation abrogated the regulatory effect of verapamil on fibroblast autophagy and fibrosis during US progression. Finally, verapamil mitigated US in vivo by activating fibroblast autophagy. CONCLUSION: Taken together, verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited fibrosis by repressing the CaMK IIδ/STAT3/PAF1 axis.

Effects of soft tissue mobilisation on subacute adherent linear scars: a single-group intervention study.

OBJECTIVE: Scar adherence due to a pathological healing process can cause physical and psychological disturbance. Soft tissue mobilisation (STM) techniques are widely used to treat and prevent scar adherence, but little is known on their effects. We aimed to analyse the effect of STM in patients with subacute post-surgical scar adhesions affecting the extremities. METHOD: A single-group quasi-experimental study was conducted on consecutive patients undergoing post-surgery limb rehabilitation. Patients with a baseline Adhesion Severity (AS) index of <0.5 at the worst scar point, as measured by the Adheremeter, were eligible. All patients who completed a minimum of five manual treatment sessions were included. The primary outcome was the AS index and the secondary outcome was the Italian version of the Patient and Observer Scar Assessment Scales (POSAS-I). RESULTS: A cohort of 19 patients underwent an average of eight STM sessions over a period of one month. The AS index value increased from a median of 0.12 at baseline (interquartile range (IQR): 0.05-0.25) to 0.41 post-treatment (IQR: 0.26-0.63; median change: 0.24; IQR: 0.16-0.40; p<0.001). A large effect size was observed for both AS and Observer Scar Assessment Scale (OSAS-I) (Cohen r=0.6), with a large probability of superiority (PS) (87% and 86%, respectively). A moderate effect was observed for the Patient Scar Assessment Scale (PSAS-I) (Cohen=0.4; PS=71%). Pre-post treatment changes exceeded the minimal detectable changes for the AS and OSAS-I in 68% of subjects, and for PSAS-I in 21% of subjects. CONCLUSION: STM manual techniques may produce a large effect on the mobility of adherent subacute post-surgical scars.

Comparison of the Cosmetic Efficacy of Extractum Cepae and Silicone-Based Gel in Upper Blepharoplasty.

BACKGROUND: Upper eyelid blepharoplasty is one of the most common surgeries performed worldwide. However, an important problem after surgery is scar formation. The authors aimed to compare the efficacy of extractum cepae and silicone-based gels on postoperative scar appearance in patients undergoing upper eyelid blepharoplasty. METHODS: After suture removal, patients were divided into 3 groups: group 1 [n=82, extractum cepae, sodium heparin, and allantoin mixture, Contractubex Gel (Merz Pharmaceuticals, Frankfurt, Germany)], group 2 [n=81, silicone-based gel (Dermatix Ultra Silicone Gel, Menarini, Singapore)], and group 3 (n=77, no additional treatment). Patients used the topical gels twice daily. All evaluations were performed on color photographs by 2 physicians during the postoperative first and third months. RESULTS: The mean visual analog scale scores were significantly higher in all 3 groups in the postoperative first month (4.39±2.03, 4.41±2.57, and 4.33±2.46, respectively) compared with the postoperative third month (2.22±1.24, 2.15±1.38, and 2.29±1.47, respectively) ( P =0.014, 0.037, and 0.026, respectively). The "Is the scar more stiff" score was higher in the postoperative first month compared with the third month. CONCLUSIONS: In conclusion, blepharoplasty scars improved up to the postoperative third month, but the topical gels used did not significantly improve the cosmetic appearance of blepharoplasty scars compared with the control group.

Ethical Considerations in Follicular Unit Excision Surgical Procedures.

Follicular unit excision (FUE) is an increasingly popular hair restoration technique. In many instances, it surpasses linear strip excision (LSE) surgery in terms of number of procedures and clinics dedicated to performing FUE. The rise in popularity relates primarily to a somewhat misguided perception that FUE produces less evidence of a surgical procedure having been performed. This is based on the fact that a linear scar is avoided. The procedure is easier to learn and "less invasive" as compared to LSE harvesting and requires less staff and capital expense. The FUE procedure is aggressively marketed often as "scarless surgery." This false statement, along with the ease of starting an FUE practice, has resulted in various ethical issues related to evaluation, methodology, and business practices. In this chapter, we discuss the ethical issues surrounding FUE hair restoration surgery and the examination of the mathematics of donor management as it relates to the ethical management of the FUE patient.

Paradigm Shift from Linear Strip to Follicular Unit Excision in Hair Restoration Surgery.

Follicular unit excision (FUE) is a very effective and valuable modality for obtaining donor hair follicles using manual, motorized, or robotic devices to harvest individual donor follicular units in situ without a linear donor scar or visible scarring making it ideal for patients who wish to wear their hair short and hide signs of surgery. Over the past two decades, FUE has become increasingly popular, and the rising demand for FUE has driven the worldwide market size of hair restoration surgery (HRS) to an unprecedented height.FUE has revolutionized the HRS industry and offers excellent cosmesis and high patient satisfaction. Unfortunately, a large part of the favorable appeal of FUE is due to false claims that it is "minimally invasive," "scarless," or "not even surgery." Most patients opt-in for FUE due to these misconceptions, which are advertised by "black-market" clinics offering low-cost FUE surgery performed by amateur, nonprofessional technicians on unsuspected patients. The technique appears deceptively simple, and many neophyte surgeons falsely believe that the learning curve of FUE is short because the barrier of entry is low and no previous surgical skill is required. Nevertheless, injuries on grafts are extremely easy to occur since FUE is a blind technique and can be minimized only with excellent technique, which takes years to master.FUE actually presents unique challenges for the surgeon and carries potential long-term permanent side effects if not performed properly. The surgeon must have a thorough understanding of the nuances of the FUE surgical technique to ensure consistent graft quality and favorable cosmesis of both donor and recipient areas. Efficient FUE requires dexterity, training, dedication, devotion, enthusiasm, cognitive clarity, scientific knowledge, experience, and an extended learning curve.FUE is an invaluable addition to the armamentarium of a hair restoration surgeon but has to be judiciously performed.

Nasal Sill Flap for Lip Lifting.

BACKGROUND: Over the years, different techniques have been developed to reduce the number of incisions and scars in subnasal lip lifting and to increase the amount of lifting. The aim of this study was to present a new technique to hide the scars at the nasal base in subnasal lip lifting procedures and to review the literature. METHODS: The file of patients who underwent subnasal lip lifting between January 2019 and January 2021 were examined. In all patients, the nasal sill flap that was designed was elevated, and the nasal sill flap that was prepared was adapted to its new location when the excision had been completed. Two different plastic surgeons evaluated the patients in the postoperative 12-month follow-ups. The scars were evaluated for vascularity, pigmentation, elasticity, thickness, and height. RESULTS: The study included 26 patients. While 21 patients had no histories of lip lifting, five patients had had previous lip lifting history. The mean operation time was 37.11 minutes. Patients' skin types were determined as Type 3 in 18 patients and Type 4 in eight patients according to the Fitzpatrick classification. The mean follow-up period of the patients was 13.11 months. At the end of the 12-month period, the mean scar score of the patients was calculated as 11.15. The mean scar score of primary cases was 11.14, and the mean scar score of secondary cases was 11.20 (p = 0.983). There was no statistically significant difference in terms of complications among smokers (p = 0.356). The mean scar score was calculated as 12.17 in patients who had Type 3 skin and 8.88 in patients with Type 4 skin (p = 0.075). CONCLUSIONS: This technique is beneficial for patients because the scars are discrete and easier for patients to accept.