Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Pharmacological and cell-based treatments to increase local skin flap viability in animal models.

Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10-15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control.

BACKGROUND: Skin flap transplantation is a routine strategy in plastic and reconstructive surgery for skin-soft tissue defects. Recent research has shown that M2 macrophages have the potential for pro-angiogenesis during tissue healing. METHODS: In our research, we extracted the exosomes from M2 macrophages(M2-exo) and applied the exosomes in the model of skin flap transplantation. The flap survival area was measured, and the choke vessels were assessed by morphological observation. Hematoxylin and eosin (H&E) staining and Immunohistochemistry were applied to assess the neovascularization. The effect of M2-exo on the function of Human umbilical vein endothelial cells (HUVECs) was also investigated. We also administrated 2-methoxyestradiol (2-ME2, an inhibitor of HIF-1α) to explore the underlying mechanism. We tested the effects of M2-Exo on the proliferation of HUVECs through CCK8 assay and EdU staining assay. RESULTS: The survival area and number of micro-vessels in the skin flaps were increased in the M2-exo group. Besides, the dilation rate of choke vessels was also enhanced in the M2-exo group. Additionally, compared with the control group, M2-exo could accelerate the proliferation, migration and tube formation of HUVECs in vitro. Furthermore, the expression of the pro-angiogenesis factors, HIF-1α and VEGFA, were overexpressed with the treatment of the M2-exo. The expression of HIF1AN protein level was decreased in the M2-exo group. Finally, treatment with HIF-1α inhibitor reverses the pro-survival effect of M2-exo on skin flaps by interfering with the HIF1AN/HIF-1α/VEGFA signaling pathway. CONCLUSION: This study showed that M2-exosomes promote skin flap survival by enhancing angiogenesis, with HIF1AN/HIF-1α/VEGFA playing a crucial role in this process.

Extramammary Paget's Disease of the Scrotal and Penile: A Case Report and Review of the Literature.

INTRODUCTION: Extramammary Paget's disease of the scrotum and penis is a relatively rare cutaneous malignant tumor. At present, its pathogenesis, and clinical and pathological characteristics are not very clear. This is controversial regarding surgical margin width to decrease the high recurrence rate. This paper aimed to report the case and review the literature of extramammary Paget's disease of scrotum and penis. CASE PRESENTATION: We presented the case of a 74-year-old male patient with the patchy erythema and pruritus in the perineum who was admitted to our department. Biopsy of the large plaque revealed Paget disease. Under the condition of ensuring negative surgical margins by rapid frozen pathology, a wide local excision of the lesion, bilateral orchiectomy, and adnexectomy were performed on the patient. Pathology revealed that many scattered vacuolated Paget cells were observed in the epidermal layer, and the diagnosis was Paget's disease of the scrotum and penis. The 2 cm outside the skin lesion was used as the initial surgical margin, and free skin flap transplantation was used to repair the surgical wound. The patient recovered well and was discharged 1 week after surgery. CONCLUSION: Currently, histopathologic biopsy is the most important diagnostic method for EMPD. Once confirmed, for patients eligible for surgical intervention, wide local excision of the lesion and rapid intraoperative frozen pathological examination should be performed as soon as possible. The skin flap transplantation is the first choice for the repair of large-scale wound after surgery.

Improved rehabilitation efficiency after cranioplasty in patients with sunken skin flap syndrome: a case series.

PURPOSE: Sunken Skin Flap Syndrome (SSFS) is an uncommon, delayed complication after craniectomy characterized by a functional plateau or decline with variable neurologic symptoms, improving after cranioplasty. SSFS negatively impacts the rehabilitation course, with subjective reports of functional improvement after cranioplasty. However, no studies have assessed the impact of cranioplasty on functional recovery rate. This case series aims to analyze SSFS manifestations and management while awaiting cranioplasty. Also, to assess the role of cranioplasty on rehabilitation outcomes and recovery rate in SSFS patients. METHODS: Four patients were identified with SSFS in inpatient rehabilitation. Each patient had unique clinical manifestations, with multiple strategies used for symptomatic control. Patients spent an average of 23 days in rehabilitation with SSFS symptoms before cranioplasty. After cranioplasty, all patients had SSFS symptom resolution. Comparing change in functional independence measure (FIM) scores and FIM efficiency pre-and post-cranioplasty rehabilitation course, a mean improvement of 23 and 0.72 occurred after cranioplasty, respectively. CONCLUSION: A diagnosis of SSFS should be considered in craniectomy patients exhibiting functional decline or plateau with associated neurological symptoms. This study suggests that FIM and FIM efficiency increases in SSFS patients after cranioplasty, supporting prompt cranioplasty to improve functional outcomes and minimize rehabilitation delays.

Tetrandrine promotes the survival of the random skin flap via the PI3K/AKT signaling pathway.

Flaps are mainly used for wound repair. However, postoperative ischemic necrosis of the distal flap is a major problem, which needs to be addressed urgently. We evaluated whether tetrandrine, a compound found in traditional Chinese medicine, can prolong the survival rate of random skin flaps. Thirty-six rats were randomly divided into control, low-dose tetrandrine (25 mg/kg/day), and high-dose tetrandrine (60 mg/kg/day) groups. On postoperative Day 7, the flap survival and average survival area were determined. After the rats were sacrificed, the levels of angiogenesis, apoptosis, and inflammation in the flap tissue were detected with immunology and molecular biology analyses. Tetrandrine increased vascular endothelial growth factor and Bcl-2 expression, in turn promoting angiogenesis and anti-apoptotic processes, respectively. Additionally, tetrandrine decreased the expression of Bax, which is associated with the induction of apoptosis, and also decreased inflammation in the flap tissue. Tetrandrine improved the survival rate of random flaps by promoting angiogenesis, inhibiting apoptosis, and reducing inflammation in the flap tissue through the modulation of the PI3K/AKT signaling pathway.

Photobiomodulation in promoting increased Skin Flap Viability: a systematic review of animal studies.

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery.

Preservation of the native urethral plate and corpus spongiosum combined with buccal mucosa graft plus Orandi's penile skin flap as an alternative to staged urethroplasty for narrow penile strictures.

OBJECTIVE: In narrow anterior urethral strictures, the combined buccal mucosa graft (BMG) with pedicled penile skin flap (PSF) represents a well-known effective alternative to staged urethroplasty. We hypothesized that if the native urethral plate and adjacent corpus spongiosum were preserved, a narrower flap would be needed, and reinforced ventral stability could be achieved without compromising the surgical outcome. METHODS: Twelve patients with narrow penile urethral strictures underwent single-stage augmentation urethroplasty using a combined technique. A BMG was quilted to the corpora cavernosa in a dorsal onlay approach, and a longitudinal ventral PSF was transposed ventrally and sutured to the scarred native urethral mucosa on one side and to the BMG on the other side to form a neourethra of triangular form. The preserved corpus spongiosum was wrapped and fixed around the flap ventrally. RESULTS: The median age was 47 years (IQR 35-59), and the median stricture length was 5 cm (IQR 3, 8-7). The median surgical time was 205 min (IQR 172-236). The overall success rate (SR) was 91.7% without sacculation or diverticula formation after a median follow-up period of 38 months (IQR 33-40). Three transient fistulas healed through prolonged urinary diversion. Five patients (41.7%) reported postvoid dribbling following urethroplasty. CONCLUSION: Preservation of the native urethral plate is a valuable adjunct to the combination of graft and flap for single-stage augmentation urethroplasty for narrow urethral strictures, with satisfactory mid-term success and an acceptable complication rate.

In Situ Monitoring and Assessment of Ischemic Skin Flap by High-Frequency Ultrasound and Quantitative Parameters.

Skin flap surgery is a critical procedure for treating severe skin injury in which post-surgery lesions must well monitored and cared for noninvasively. In the present study, attempts using high-frequency ultrasound imaging, quantitative parameters, and statistical analysis were made to extensively assess variations in the skin flap. Experiments were arranged by incising the dorsal skin of rats to create a skin flap using the chamber model. Measurements, including photographs, 30 MHz ultrasound B-mode images, skin thickness, echogenicity, Nakagami statistics, and histological analysis of post-surgery skin flap, were performed. Photograph results showed that color variations in different parts of the skin flap may readily correspond to ischemic states of local tissues. Compared to post-surgery skin flap on day 7, both integrated backscatter (IB) and Nakagami parameter (m) of the distal part of tissues were increased, and those of the skin thickness were decreased. Overall, relative skin thickness, IB, and m of the distal part of post-surgery skin flap varied from 100 to 67%, -66 to -61 dB, and 0.48 to 0.36, respectively. These results demonstrate that this modality and quantitative parameters can be feasibly applied for long-term and in situ assessment of skin flap tissues.

Prospective Clinical Trial for Predicting Mastectomy Skin Flap Necrosis with Indocyanine Green Angiography in Implant-Based Prepectoral Breast Reconstruction.

BACKGROUND: Indocyanine green angiography (ICG-A) is a useful tool for evaluating mastectomy skin flap (MSF) perfusion during breast reconstruction. However, a standardized protocol for interpreting and applying MSF perfusion after mastectomy has not been established yet. The purpose of this study is to establish criteria for assessing MSF perfusion in immediate implant-based prepectoral breast reconstruction while correlating ICG-A findings with postoperative outcomes METHODS: This prospective observational study was conducted at a single institution and involved patients with breast cancer who underwent mastectomy and immediate implant-based prepectoral breast reconstruction between August 2021 and August 2023. The terms "hypoperfused flap" and "hypoperfused area" were defined according to ICG-A perfusion. MSF exhibited < 30% perfusion, excluding the nipple and the corresponding region, respectively. Data on the hypoperfused flap, hypoperfused area, and MSF necrosis were collected. RESULTS: Fifty-three breast cases were analyzed. Eight patients developed MSF necrosis (15.1%, 8/53). Of these, two patients underwent surgical debridement and revision within 3 months (3.8%, 2/53). There were nine cases of a hypoperfused flap, eight of which developed MSF necrosis. The hypoperfused flap was a significant predictor of the occurrence of MSF necrosis (p < 0.001). There was a tendency for increased full-thickness necrosis with a wider hypoperfused area. CONCLUSIONS: The hypoperfused flap enabled the prediction of MSF necrosis with high sensitivity, specificity, positive predictive value, and negative predictive value. Considering the presumed correlation between the extent of the hypoperfused area and the need for revision surgery, caution should be exercised when making intraoperative decisions regarding the reconstruction method. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF.

BACKGROUND: Distal necrosis and inflammation are two of the most common health consequences of random-pattern skin flaps survival (SFS). Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the nitric oxide molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the SFS and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena. METHODS: Each rat was pretreated with either a vehicle (control) or various doses of spermidine (0.5, 1, 3, 5, 10 and 30 mg/kg) and then was executed a random-pattern skin flap paradigm. Also, spermidine at the dose of 5 mg/kg was selected and one group rats received spermidine 20 min prior to surgery and one additional dose 1 day after operation. Then, 7 days after operations, interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), and nitrite levels were inquired in the tissue samples by ELIZA kit. Vascular endothelial growth factor expression was assessed by DAPI staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine, and cadaverine, were analyzed using HPLC. RESULTS: Pretreatment with spermidine 5 mg/kg improved SFS considerably in microscopic skin H&E staining analysis and decreased the percentage of necrotic area. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of nitric oxide and reducing inflammatory cytokines. CONCLUSIONS: Spermidine could improve skin flaps survival, probably through the nitrergic system and inflammation pathways. This preclinical study provides level III evidence for the potential therapeutic effects of spermidine on SFS in rats, based on the analysis of animal models. Further studies are needed to confirm these findings in clinical settings. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparative study of optimal compression pressure between conventional Barton's dressing and prefabricate garment in parotidectomy patients.

Excessive compression after parotidectomy can lead to flap necrosis, while inadequate pressure can cause fluid accumulation. This study aimed to determine the optimal pressure and compression properties of different types of dressings. Initially, pressure measurements were taken for conventional Barton's dressing and a pre-fabricated facial garment. In the subsequent phase, patients were randomly assigned to receive one of three types of pressure dressings: conforming bandage Barton's dressing, elastic bandage Barton's dressing or pre-fabricated facial garment. The dressing types were randomly crossed over the following day. The mean pressure exerted by conventional Barton's dressing and the pre-fabricated facial garment was 15.86 and 14.81 mmHg, respectively. There was no significant difference in the proportion of optimal pressure among the three types of pressure dressing (p-values of 0.195, 0.555 and 0.089 at pre-auricular, angle of mandible and post-auricular sites, respectively). The pre-auricular area demonstrated the highest proportion of optimal pressure, while suboptimal pressure was noted at the angle of the mandible and post-auricular area. Dressing types had no effect on pressure stability (p = 0.37), and there was no significant difference in patient preference (p = 0.91). Conforming bandage Barton's dressing, elastic bandage Barton's dressing and pre-fabricated facial garment exhibit comparable compressive properties, with no significant difference in patient preference and pressure stability.

Evaluating the efficacy of combined flap coverage, antibiotic-loaded bone cement and negative pressure irrigation in traumatic osteomyelitis management.

Traumatic osteomyelitis with accompanying soft tissue defects presents a significant therapeutic challenge. This prospective, randomised controlled trial aims to evaluate the efficacy of antibiotic-impregnated bone cement, flap coverage and negative pressure sealed irrigation in the management of traumatic osteomyelitis complicated by soft tissue defects. A total of 46 patients with clinically diagnosed traumatic osteomyelitis and soft tissue defects were randomised into a control group (n = 23) and an observation group (n = 23). The control group underwent standard flap coverage and negative-pressure lavage, while the observation group received an additional treatment with antibiotic-loaded bone cement. Efficacy was measured based on clinical criteria, surgical metrics and morphometric assessment of bone and soft tissue defects. Statistical analyses were performed using SPSS version 27.0. The observation group, treated with an integrated approach of flap coverage, negative pressure wound therapy (NPWT) and antibiotic-impregnated bone cement, demonstrated significantly higher overall treatment efficacy (91.3%) compared to the control group, which received only flap coverage and NPWT (65.2%) (p < 0.01). This enhanced efficacy was evidenced through various outcomes: the observation group experienced reduced surgical times, shorter hospital stays, fewer dressing changes and accelerated wound healing, all statistically significant (p < 0.001). Additionally, a quantitative analysis at 6-month post-treatment revealed that the observation group showed more substantial reductions in both bone and soft tissue defect sizes compared to the control group (p < 0.001). The multi-modal treatment strategy, combining skin flap coverage, antibiotic bone cement and negative-pressure irrigation, showed marked efficacy in treating traumatic osteomyelitis and associated soft tissue defects. This approach accelerated postoperative recovery and lowered costs.

Design and localization algorithm of flap guide plate for jaw defect based on digital 3D printing.

The anterolateral thigh flap is often used to repair the wound tissue defect. Because it is difficult to carry out the perforating vessels before and after the operation, it is considered to use digital design combined with 3D printing technology to prepare the digital three-dimensional guide plate, and at the same time, the guide plate positioning algorithm is designed according to the error caused by the different placement of the guide plate at the site to be transplanted. First of all, select the patients with jaw defect, make the patient's jaw model, obtain the corresponding plaster working model through 3D scanning, obtain STL data, design the guide plate in combination with Rihnoceros and other software, and print the flap guide plate corresponding to jaw defect with the help of metal powder using 3D printer. Based on sequential CT images, the localization algorithm takes the improved genetic algorithm as the research object, extracts the information of the transplantation area as the parameter space, codes the parameters such as the coordinates of the end points of the flap transplantation, and constructs the target function and fitness function of the transplantation. In the experiment, the soft tissue of the patients with jaw defects can be well repaired based on the guide plate. The positioning algorithm locates the flap graft under the condition of less environmental parameters, and obtains the corresponding diameter parameters.

Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia-reperfusion injury via mTOR/ULK1/FUNDC1 pathways.

Flap necrosis, the most prevalent postoperative complication of reconstructive surgery, is significantly associated with ischaemia-reperfusion injury. Recent research indicates that exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold potential therapeutic applications in several diseases. Traditionally, BMSCs are cultured under normoxic conditions, a setting that diverges from their physiological hypoxic environment in vivo. Consequently, we propose a method involving the hypoxic preconditioning of BMSCs, aimed at exploring the function and the specific mechanisms of their exosomes in ischaemia-reperfusion skin flaps. This study constructed a 3 × 6 cm2 caudal superficial epigastric skin flap model and subjected it to ischaemic conditions for 6 h. Our findings reveal that exosomes from hypoxia-pretreated BMSCs significantly promoted flap survival, decrease MCP-1, IL-1ß, and IL-6 levels in ischaemia-reperfusion injured flap, and reduce oxidative stress injury and apoptosis. Moreover, results indicated that Hypo-Exo provides protection to vascular endothelial cells from ischaemia-reperfusion injury both in vivo and in vitro. Through high-throughput sequencing and bioinformatics analysis, we further compared the differential miRNA expression profiles between Hypo-Exo and normoxic exosomes. Results display the enrichment of several pathways, including autophagy and mTOR. We have also elucidated a mechanism wherein Hypo-Exo promotes the survival of ischaemia-reperfusion injured flaps. This mechanism involves carrying large amounts of miR-421-3p, which target and regulate mTOR, thereby upregulating the expression of phosphorylated ULK1 and FUNDC1, and subsequently further activating autophagy. In summary, hypoxic preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of BMSC-derived exosomes in the treatment of flap ischaemia-reperfusion injury.

Nipple-areolar complex (NAC) or skin flap ischemia necrosis post nipple-sparing mastectomy (NSM)-analysis of clinicopathologic factors and breast magnetic resonance imaging (MRI) features.

BACKGROUND: The purpose of this study is to identify clinicopathologic factors and/or preoperative MRI vascular patterns in the prediction of ischemia necrosis of the nipple-areola complex (NAC) or skin flap post nipple-sparing mastectomy (NSM). METHODS: We performed a retrospective analysis of 441 NSM procedures from January 2011 to September 2021 from the breast cancer database at our institution. The ischemia necrosis of NAC or skin flap was evaluated in correlation with clinicopathologic factors and types of skin incision. Patients who received NSM with preoperative MRI evaluation were further evaluated for the relationship between vascular pattern and the impact on ischemia necrosis of NAC or skin flap. RESULTS: A total of 441 cases with NSM were enrolled in the current study, and the mean age of the cases was 49.1 ± 9.8 years old. A total of 41 (9.3%) NSM procedures were found to have NAC ischemia/necrosis. Risk factors were evaluated of which old age, large mastectomy specimen weight (> 450 g), and peri-areola incision were identified as predictors of NAC necrosis. Two-hundred seventy NSM procedures also received preoperative MRI, and the blood supply pattern was 18% single-vessel type and 82% double-vessel pattern. There were no correlations between MRI blood supply patterns or types of skin flap incisions with ischemia necrosis of NAC. There were also no correlations between blood loss and the pattern or size of the blood vessel. CONCLUSION: Factors such as the type of skin incision, age, and size of mastectomy weight played an important role in determining ischemia necrosis of NAC; however, MRI vascular (single or dual vessel supply) pattern was not a significant predictive factor.

Onlay Pedicled Transverse Skin Flap versus One-Stage Inlay Buccal Mucosal Graft in Penile Urethroplasty: A Prospective Matched-Pair Analysis.

INTRODUCTION: The aim of this study was to compare urethroplasty using onlay pedicled transverse skin flap (PSF) versus one-stage inlay buccal mucosa graft (BMG) in repair of penile urethral strictures. METHODS: We conducted a prospective matched-pair analysis of 44 male patients receiving penile urethroplasty between June 2016 and June 2019. There were 22 patients who received PSF and 22 patients who received BMG. Matching was performed according to stricture length. Patients with strictures caused by lichen sclerosus, prior hypospadias repair, or failed prior urethroplasty were excluded. Treatment was considered successful if no recurrence was observed. Successful repair, complication rates, patients' satisfaction, and quality of life improvement were endpoints of this study. RESULTS: Mean follow-up was 40.3 months. PSF and BMG showed comparable success rates (90.9% vs. 86.4%, p = 0.713). Recurrent stricture occurred in 2 patients (9.1%) who received PSF and in 3 patients (13.6%) who received BMG. Operation time was significantly longer for PSF than for BMG (108.4 min vs. 78.1 min, p = 0.01). Univariable logistic regression analysis revealed no relevant risk factors for stricture recurrence. CONCLUSION: Early results indicate comparable success rates of PSF and BMG in penile urethroplasty. Further studies with larger sample size and longer follow-up periods are required to evaluate subtle differences between both techniques.

Baicalin promotes random-pattern skin flap survival by inducing autophagy via AMPK-regulated TFEB nuclear transcription.

The random-pattern skin flap is a generally used technique to cover the soft tissue defect, while its application is often constrained by complications after the flap transplant. Necrosis of the flap remains a principal obstacle. The purpose of this study was to investigate the effect of Baicalin on skin flap survival and its mechanism. First of all, we discovered that administering Baicalin stimulated cell migration and boosted the formation of capillary tubes in human umbilical vein endothelial cells. Then, we detected that Baicalin reduced apoptosis-induced oxidative stress by using western blot and oxidative stress test kit. After that, we observed that Baicalin increased autophagy and utilized 3MA to block autophagy augmentation substantially reversing the effects of Baicalin therapy. Furthermore, we uncovered the underlying mechanisms of Baicalin-induced autophagy via AMPK-regulated TFEB nuclear transcription. Finally, our in vivo experiment findings showed that Baicalin reduces oxidative stress, inhibits apoptosis, promotes angiogenesis, and boosts the levels of autophagy. After autophagy was blocked, substantially reversing the effects of Baicalin therapy. Our study indicated that Baicalin-induced autophagy via AMPK regulated TFEB nuclear transcription and then promotes angiogenesis and against oxidative stress and apoptotic promotes skin flap survival. These findings highlight the therapeutic potential for the clinical application of Baicalin in the future.

IL-4 modified expanded polytetrafluoroethylene (e-PTFE) surgical patch promotes angiogenesis in transplanted flap and inhibits inflammatory response.

Skin flap transplantation is one of the most common tissue transplantation methods for wound repair and organ reconstruction in plastic surgery. During the transplantation process, the inflammatory response of transplanted flap and angiogenesis are critical to the successful rate of skin flap transplantation. In recent years, to improve the biocompatibility and cell affinity of biomedical materials, the modified biomaterials have gradually become a popular subject in scientific researches. In our study, the IL-4 modified expanded polytetrafluoroethylene (e-PTFE) surgical patch IL4-e-PTFE was prepared, and the rat skin flap transplantation model was constructed. The results of cell experiment prove that IL-4 has potentiation in the angiogenesis of human umbilical vein endothelial cell (HUVEC) induced by monocyte, and IL-4 can also promote angiogenesis by inducing the M2 macrophages. According to the results of in vivo experiment, the apoptosis level of transplanted flap cells of rats in the IL4-e-PTFE group was lower than that in the e-PTFE group, and in the IL4-e-PTFE group, the expression levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α showed significantly decline compared to the e-PTFE group, while the expression levels of anti-inflammatory cytokines IL-1Ra, IL-10 and TGF-ß presented significant increase compared to the e-PTFE group; the immunofluorescence staining results show that the number of M2 macrophages in transplanted flap area of rats in the IL4-e-PTFE group was significantly higher than that in the e-PTFE group, and the angiogenesis level was remarkably improved. In this study, by preparing IL4-e-PTFE and carrying out the cell and in vivo experiments, a reference method is proposed, which can reduce the inflammatory response during skin transplantation process using e-PTFE and optimize the long-term effects of flap blood vessels, hoping to provide a broader space for the applications of e-PTFE in medicine.