Emodin activates autophagy to suppress oxidative stress and pyroptosis via mTOR-ULK1 signaling pathway and promotes multi-territory perforator flap survival.

BACKGROUND: Multi-territory perforator flap reconstruction has been proven effective in treating large skin and soft tissue defects in clinical settings. However, in view of that the multi-territory perforator flap is prone to partial postoperative necrosis, increasing its survival is the key to the success of reconstruction. In this study, we aimed to clarify the effect of emodin on multi-territory perforator flap survival. METHODS: Flap survival was assessed by viability area analysis, infrared laser imaging detector, HE staining, immunohistochemistry, and angiography. Western blotting, immunofluorescence assays, and real-time fluorescent quantitative PCR were performed to detect the indicators of oxidative stress, pyroptosis and autophagy. RESULTS: After emodin treatment, the multi-territory perforator flap showed a significantly increased survival rate, which was shown to be closely related to the inhibition of oxidative stress and pyroptosis and enhanced autophagy. Meanwhile, the use of autophagy inhibitor 3 MA was found to reverse the inhibitory effects of emodin on oxidative stress and pyroptosis and weaken the improving effect of emodin on flap survival, suggesting that autophagy plays a critical role in emodin-treated flaps. Interestingly, our mechanistic investigations revealed that the positive effect of emodin on multi-territory perforator flap was attributed to the mTOR-ULK1 signaling pathway activation. CONCLUSIONS: Emodin can inhibit oxidative stress and pyroptosis by activating autophagy via the mTOR-ULK1 pathway, thereby improving the multi-territory perforator flap survival.

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.

Free vascularized bone graft from the lateral epicondylar region of the humerus for treatment of scaphoid nonunion.

BACKGROUND: Free vascularized bone grafting (FVBG) has become one of the essential methods for treating scaphoid nonunion complicated by avascular necrosis. However, commonly used bone graft, including the medial femoral condyle bone graft and iliac crest bone graft, still present challenges such as a high rate of donor site complications and variations of vascular pedicle. In this study, we have introduced a novel bone graft-the lateral humeral condyle bone graft with the posterior branch of the radial collateral artery (PBRCA) as the vascular pedicle-as an alternative option, with the aim of overcoming some of the limitations of previously described FVBG procedures. METHODS: Nine patients who had a nonunion of the scaphoid that had been present for an average of 16.8 months (range 9-35 months) were managed with use of a free vascularized bone graft obtained from the lateral humeral epicondylar region. Avascularity of the scaphoid, as assessed on preoperative magnetic resonance imaging and intraoperative bone marrow puncture test. Postoperatively, regular X-ray and CT scans examinations were conducted to assess the progress of fracture healing. Active motion of the wrist, and grip strength recovery were measured periodically. Wrist pain was graded using the Visual Analogue Scale (VAS), while wrist joint functionality was evaluated using the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaire and the Patient-Rated Wrist Evaluation (PRWE) scale. The elbow functional outcome was evaluated by the Mayo Elbow Performance Score (MEPS). RESULTS: All of nine lateral humeral epicondylar bone grafts were successfully harvested. The blood supply of the graft during surgery was excellent in six cases and good in three cases. The size of the bone grafts ranges from 1.0 cm × 0.5 cm × 0.5 cm to 2.0 cm × 1.0 cm × 0.5 cm. The average vascular pedicle length was 3.4 cm (range 2.0-6.0 cm). There were no early complications in either the donor or recipient areas after surgery. Union was successfully achieved in all nine patients, with an average time to union of 14.3 weeks (range 11-20 weeks) after surgery. The average follow-up period was 31.2 months (range 26-40 months). At the final follow-up, the average palmar flexion, dorsal extension, radial deviation, and ulnar deviation angles of the injured wrist joint were 56.1° (range 45°-70°), 56.1° (range 40°-80°), 10.6° (range 5°-20°), and 22.2° (range 15°-35°), respectively, which reached 79.0%, 82.1%, 59.4%, and 72.8% of the average activity of the contralateral normal side. The average grip strength of the injured side was 35.2 kg (range 22-51 kg), which was equivalent to 81.3% of the average grip strength of the contralateral side. The average VAS score for wrist joint pain was 1.0 point (range 0-2 points); the Quick-DASH score was 9.2 points (range 6-18 points); and the PRWE score was 13.1 points (range 9-16 points), the Mayo Elbow Performance Index was 100 points (range 100-100 points). One patient reported a feeling of friction during movement but no pain. One patient reported numbness in the donor site. One patient complained of pain when applying force to the scar in the donor area. During the follow-up period, these complications showed improvement without any treatment. CONCLUSION: The FVBG technique has been considered an effective method for treating scaphoid nonunion with avascular necrosis. Compared to traditional FVBG, the lateral humeral epicondylar bone graft exhibits a higher union rate, fewer complications, and easier accessibility, making it a favorable choice.

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

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.

The rare complication of vascular malformations of the limb after sclerotherapy: a report of 3 cases and brief literature review.

BACKGROUND: Vascular malformations are common but complicated types of disease in infants, with unclear causes and lack of effective prevention. The symptoms usually do not disappear and tend to progress without medical intervention. It is extremely necessary to choose correct treatment options for different types of vascular malformations. A large number of studies have confirmed that sclerotherapy has a tendency to become the first-line treatment in near future, but it is also associated with mild or severe complications. Furthermore, to our knowledge, the serious adverse event of progressive limb necrosis has not been systematically analyzed and reported in the literature. CASE PRESENTATION: Three cases (two females and one male) were presented who were all diagnosed as vascular malformations and were treated by several sessions of interventional sclerotherapy. Their previous medical records showed the use of several sclerosants in different sessions including Polidocanol and Bleomycin. The sign of limb necrosis did not occur during the first sclerotherapy, but after the second and third sessions. Furthermore, the short-term symptomatic treatment could improve the necrosis syndrome, but could not change the outcome of amputation. CONCLUSION: Sclerotherapy undoubtedly tends to be the first-line treatment in near future, but the adverse reactions still remain major challenges. Awareness of progressive limb necrosis after sclerotherapy and timely management by experts in centers of experience of this complication can avoid amputation.

The application of infrared thermography technology in flap: A perspective from bibliometric and visual analysis.

The application of infrared thermography technology (IRT) in flap has become a major focus of research, as it provides a non-invasive, real-time, and quantitative approach for monitoring flap perfusion. In this regard, we conducted a comprehensive visualization and scientometric analysis to systematically summarize and discuss the current state of research in this field. We systematically reviewed publications on the application of IRT in flap procedures from 1999 to 2022, using the Web of Science Core Collection (WoSCC). Through scientometric analysis, we examined annual trends, affiliations, countries, journals, authors, and their relationships, providing insights into current hotspots and future developments in this area. We analysed 522 English studies and found a steady increase in annual publications. The United States and Germany had the highest publication rates, with Beth Israel Deaconess Medical Center and Shanghai Jiaotong University being leading institutions. Notably, Lee BT and Alex Keller emerged as influential authors in this field. Compared to existing techniques, infrared-based technology offers significant advantages for non-invasive monitoring of flap perfusion, including simplicity of operation and objective results. Future trends should focus on interdisciplinary collaborations to develop new infrared devices and achieve intelligent image processing, enabling broader application in various clinical scenarios. This bibliometric study summarizes the progress and landscape of research on 'the Application of infrared thermography technology in flap' over the past two decades, providing valuable insights and serving as a reliable reference to drive further advancements and spark researchers' interest in this field.

The free chimeric medial sural artery perforator flap for individualised and three-dimensional reconstruction of complex soft-tissue defects in extremities.

Trauma or lesion resection often causes complex wounds with deep soft tissue defects in extremities. Simply covering with a skin flap will leave a deep dead space resulting in infection, non-healing wounds, and poor long-term outcomes. Thus, effectively reconstructing complex wounds with dead space leaves a clinical challenge. This manuscript presents our experience using chimeric medial sural artery perforator (cMSAP) flap, to reconstruct complex soft tissue defects of the extremities, thereby exploring broader analysis and indications for future reference. Between March 2016 and May 11, 2022, patients (8 males and 3 females) with a mean age of 41 years (range from 26 to 55 years) underwent reconstructive surgery with the cMSAP flap. The cMSAP flap consists of an MSAP skin paddle and a medial sural muscle paddle. The size of the MSAP skin paddle ranged between 9 × 5 cm and 20 × 6 cm, and the size of the medial sural muscle paddle ranged between 2 × 2 cm and 14 × 4 cm. Primary closure of the donor site was achieved in all cases. Of the 11 patients, the cMSAP flap survived in 10 cases. The vascular compromise occurred in one special case and was treated with surgical procedures. The mean follow-up duration was 16.5 months (range of 5-25 months). Most patients present satisfactory cosmetic and functional results. The free cMSAP flap is a good option for reconstructing complex soft tissue defects with deep dead space in extremities. The skin flap can cover the skin defect, and the muscle flap can fill the dead space against infection. In addition, three types of cMSAP flaps can be used in a broader range of complex wounds. This procedure can achieve an individualised and three-dimensional reconstruction of the defects and minimise the donor site morbidities.

Small extracellular vesicles derived from PD-L1-modified mesenchymal stem cell promote Tregs differentiation and prolong allograft survival.

We aimed to explore whether programmed cell death protein-1 ligand (PD-L1) modification on small extracellular vesicles (sEVs) could promote T regulatory cells (Tregs) differentiation. In this study, it was confirmed that under physiological conditions, PD-L1 expression was minimal in the MSCs and absent in the MSC-sEVs. A vector harboring the PD-L1 gene was constructed and transfected into bone marrow mesenchymal stem cells (BM-MSCs). By extracting the sEVs of these modified BM-MSCs and monitoring the expression of the PD-L1 protein, however, PD-L1 expression was substantially increased in the MSCs and concentrated in the sEVs. Then, the rat naïve CD4 + T cells were cocultured with the sEVs derived from the PD-L1-modified MSCs (sEVsPD-L1). By flow cytometry, a higher percentage of Tregs and anti-inflammatory downstream cytokines (including IL-2, IFN-γ, TGF-ß, IL-10) was detected in the sEVsPD-L1 group than that in the control group treated by either sEVs in wild type, modified by empty vector, or blank control. Suppressive effect on CD4 + T cell proliferation serves as additional evidence to support the immunoregulation capacity of sEVsPD-L1. The animal model of vascularized composite allograft further confirmed that PD-L1-modified sEVs induce an immune tolerance, by clinically observation, histopathology, T cell fate and cell product. In conclusion, sEVsPD-L1 efficiently promotes Treg cell differentiation in vitro and in vivo, which suggests their therapeutic potential in the treatment of allograft rejection.

Large wounds reconstruction of the lower extremity with combined latissimus dorsi musculocutaneous flap and flow-through anterolateral thigh perforator flap transfer.

BACKGROUND: Management of large wounds of the lower extremities remains a challenge for plastic and reconstructive surgeons. Herein, a surgical technique and clinical algorithm using the combined transfer of a latissimus dorsi (LD) musculocutaneous flap and flow-through anterolateral thigh (ALT) perforator flap for the treatment of extensive soft-tissue defects is described. METHODS: From January 2012 to September 2018, 12 patients (six men and six women) aged 6-37 years, sustained injuries in road traffic accidents with large soft-tissue defects in the lower extremities. Seven cases were Gustillo Anderson type IIIB open fractures and two cases were Gustillo Anderson type IIIC open fractures. Two wounds were located in the knee joint, four in the calf, and six in the ankle and foot. The skin defect size ranged from 25 × 20 cm2 to 36 × 25 cm2 . All patients in this series underwent reconstruction using combined transfer of the LD musculocutaneous flap and flow-through ALT perforator flap, wherein the LD was attached through its pedicle to the distal continuation of the ALT flap. RESULTS: The size of the flow-through ALT perforator flaps ranged from 13.5 × 6.5 cm2 to 31 × 8.5 cm2 . The size of the LD musculocutaneous skin paddle ranged from 25 × 6 cm2 to 34 × 7 cm2 , and that of the muscle paddle ranged from 13 × 3.5 cm2 to 30 × 11 cm2 . One patient experienced postoperative thrombosis of the venous pedicle, and the flap was salvaged after emergency re-exploration and thrombectomy. No other complications were observed postoperatively. The mean follow-up period was 26.8 months. All patients were able to ambulate independently at the end of the follow-up period. CONCLUSIONS: The combined transfer of the LD musculocutaneous flap and flow-through ALT perforator flap ensured adequate surface coverage, making it a feasible procedure for large soft-tissue defects.

A 3D visualization layered anatomy for acromial arterial rete and flap design.

BACKGROUND: The acromial arterial rete (AAR) is the junction between the skin blood supply of the cervical side and that of the upper arm, and it is the only site crossed by the trans-regional blood supply of the cervico-humeral flap (CHF). The aim of this study was to explore the structures of AAR to optimizing flap design. METHODS: A body arteriography and spiral CT scan were performed on 33 whole adult corpses. The 3D reconstruction was used to perform continuous digital layered anatomy of the shoulder and upper chest; the acromion and acromioclavicular joint were used as the center to observe the source, route and distribution characteristics of a perforating branch and their anastomosis. RESULTS: The perforating branches were separated from an acromial branch of the transverse cervical artery (97%), posterior humeral circumflex artery (95%), a deltoid branch of the thoracoacromial artery (95%), and the acromial branch of the thoracoacromial artery (93%). The diameter of the acromial branch of the transverse cervical artery at its initial location was 1.18 ± 0.37 mm; the trunk length was 12.53 ± 3.83 cm, and it was anastomosed with other blood vessels in three forms. CONCLUSION: Deep fascia should be included in the flap design. Three kinds of pedicled transfer flaps can be designed with the acromial branch of transverse carotid artery as the vascular pedicle. Free flaps can be designed with the acromial branch of thoracoacromial artery as the vascular pedicle.

Clinical application of polyfoliate anterolateral thigh perforator flap with single-perforator. / 旋股外侧动脉降支单穿支分叶皮瓣的临床应用.

OBJECTIVES: The polyfoliate anterolateral thigh perforator flap needs to dissect two or more perforators, which is an ideal choice for repairing wide and irregular wounds. However, the uncertainty of perforating vessels restricts the development of this operation. This study discusses the feasibility and clinical efficacy of the polyfoliate anterolateral thigh perforator flap with single-perforator. METHODS: Fifteen patients with skin and soft tissue defects in extremities, were treated with polyfoliate anterolateral thigh perforator flap with single-perforator. Based on the perforator detected by Doppler ultrasound or color Doppler ultrasonography before operation, a polyfoliate anterolateral thigh perforator flap with single-perforator was designed. The perforating point of perforator was near the boundary of the skin paddle. Following the perforating vessels and vascular pedicles free, the vessels in the deep layer of the superficial fascia were meticulously free under the microscope. After obtaining the appropriate length, the skinpaddles were separated and recombined. After confirming the blood supply of flap, the vascular pedicle was ligated and transplanted to the recipient area. RESULTS: In 15 cases, the area of the flap was 8.0 cm×5.0 cm+6.0 cm×5.5 cm to 16.0 cm× 9.5 cm+24.0 cm×9.0 cm. All flaps survived well without necrosis and had a satisfactory appearance. The donor area was closed directly. The patients were followed up for 3 to 12 months, with an average of 6 months. The skin flaps were normal in color and good in texture. CONCLUSIONS: It's a better method to repair the skin and soft tissue defects in extremities by the polyfoliate anterolateral thigh perforator flap with single-perforator because only one perforator needs to be dissected, a group of blood vessels need to be anastomosed, and only one donor area needs to be sacrificed.

Anatomic Study and Clinic Application of Transverse Circumflex Scapular Artery Perforator Flap Repair of Lower Limb Soft Tissue Defects in Children.

PURPOSE: The aim of this study was to demonstrate the viability of the transverse circumflex scapular artery perforator flap (TCSAPF) in children with soft tissue defects of the lower limb. METHODS: In an anatomic study, 25 fresh cadavers were injected with lead oxide-gelatin for spiral computed tomography and 3-dimensional image reconstruction. In a 3-year clinical application study, children with soft tissue defects and exposed tendons and/or bones in the lower limb underwent free-TCSAPF repair of the defect. RESULTS: Perforators from the transverse branch of the circumflex scapular artery were identified in both anatomical and clinical studies. The average external diameter was 0.9 ± 0.3 mm. Each perforator supplied an average area of 63.5 ± 16.8 cm in anatomical. Twenty-one children were included in this group (9 boys, 12 girls, mean age, 6.6 ± 2.7 years). The size of the flaps ranged from 6 to 17 cm × 4.5 to 7 cm (average, 65.3 ± 22.6 cm). The average flap harvesting time was 30.1 ± 8.5 minutes, average operation time was 138.6 ± 31.5 minutes, and average blood loss was 89.5 ± 21.9 mL. The average length of the vessel pedicle was 8.2 ± 2.4 cm. Arterial congestion occurred in one child, 18 hours postoperatively; subsequent re-exploration and great saphenous vein transplantation were successful. Of the 3 children who had bulky flaps, 1 patient underwent defatting. Satisfactory outcomes included good appearance and function of the recipient and donor areas. CONCLUSIONS: The TCSAPF provides high-quality skin and vessel flexibility, providing a reliable blood supply in children. The flap has potential benefits over existing perforator flaps.

Complication of osteo reconstruction by utilizing free vascularized fibular bone graft.

The success of free vascularized fibular bone graft (FVFBG) has accelerated the osteo reconstruction which results from trauma, resection of a tumor or an infectious bone segment, or correction of congenital deformity. But the complication behind should not be overlooked. The failure could necessitate a second surgery, which prolong the rehabilitation period and produce further health cost. Worst, the patients may suffer a permanent impaired ankle function, or a sustained morpho-functional loss on reconstructive area which are hard to save. To provide an overview of the complication related to reconstruction by FVFBG, a narrative review is conducted to identify the complications including their types and rates, the contributing factors, the approaches to measure and the techniques to avoid. Methodologically, by quick research on Pubmed and abstract reading of reviews, we characterize five reconstructive areas where FVFBG were most frequently applied: extremities, mandible, spine, osteonecrosis of femoral head, and penile. Following, the complications on different reconstructive areas are retrieved, studied and presented in five (or more specifically, six) separate sections. By the way, meaningful difference between FVFBG and other bone flap was presented in a few words if necessary. Donor-site morbidities were studied and summarized as a whole. In these literatures, the evidences documented on limb and mandibular reconstruction have the fullest detail, followed by the spine and lastly the penile. In conclusion, FVFBG, though a mature technique, needs further deep and comprehensive study and maybe device-based assistance to achieve better reconstructive effect and minimize donor-site damage.

Use of a sequential chimeric perforator flap for one-stage reconstruction of complex soft tissue defects of the extremities.

BACKGROUND: One-stage reconstruction of complex soft tissue defects of the extremities is a challenging problem. Repair of complex soft tissue defects requires adequate skin tissues to cover the large surface wound and special tissues for obliterating the dead space. The chimeric flap is one of the most popular approaches for reconstruction of complex soft tissue defects. However, the problems of donor-site morbidity and inability to repair very large defects at one-stage remain. The purpose of this study was to present our clinical experience using sequential chimeric perforator flaps for reconstruction of complex extremity defects with primary closure of the donor site. METHODS: From August 2013 to March 2017, 12 patients with complex soft tissue defects underwent extremity reconstruction using sequential chimeric perforator flaps, which were composed of a chimeric anterolateral thigh perforator (ALTP) flap and an additional free perforator flap. The skin paddles were placed side-by-side to cover the large surface soft tissue defects, and the muscle component was used to obliterate the dead space. Of these patients, one was injured by a crushing accident, while the other 11 patients were injured in traffic accidents. RESULTS: The size of the skin paddles ranged from 26 cm × 8 cm-10 cm × 6 cm to 30 cm × 8.5 cm-29 cm × 9 cm. The muscle paddle size ranged from 2 cm × 3 cm × 4 cm to 22 cm × 4 cm × 2 cm. All-components of the sequential chimeric flaps survived in all-patients. Vascular compromise was observed in one case. One case suffered minor wound-edge necrosis and was treated conservatively. Primary closure of donor-site was successfully achieved in all-patients, and all-donor-site wounds healed uneventfully. The mean follow-up time was 15.25 months. Most of the cases showed a satisfactory contour, and only two patients presented with mildly bulky appearance that treated with a debulking procedure. CONCLUSIONS: The sequential chimeric perforator flap is an alternative procedure for reconstruct complex soft tissue defects of the extremities. This approach allows for flexible design, a larger cutaneous area, and low donor site morbidity.

Versatile design of compound vastus lateralis muscle and anterolateral thigh musculocutaneous perforator free flaps for customized reconstruction of complex skin and soft tissue defects in the extremities.

BACKGROUND: Compound anterolateral thigh flaps are popular for three-dimensional reconstruction of complex soft tissue defects. We present our 10-year experience using compound vastus lateralis (VL) muscle and anterolateral thigh musculocutaneous perforator (ALTP) flaps, and introduce three versatile customizations of this flap for individualized reconstruction of complex three-dimensional soft tissue defects. METHODS: From May 2008 to June 2017, compound VL muscle and ALTP flaps were performed in 67 consecutive patients aged 14-75 years (62 men and 5 women). The defects were in either the lower (n = 53) or upper extremity (n = 14), and ranged in size from 8 × 4 cm2 to 25 × 6 cm2. Dead space volume ranged from 4 × 2 × 1 cm3 to 20 × 3 × 2 cm3, and all flaps were harvested from patients' thighs as one of three types. In type A, a single perforator supplied both the skin and muscle components, with the vascular bundle penetrating the muscle component. In type B, a single perforator supplied both skin and muscle components with separate branches to the skin and muscle. In type C, separate vessels supplied the skin and muscle. RESULTS: In the 67 patients, 65 flaps survived, and the donor site was closed directly. Vascular compromise occurred in four patients on the first postoperative day. Two flaps were salvaged after emergency re-exploration. Flap loss occurred in two patients, and these defects were repaired using other flaps. The follow-up period ranged from 8 to 60 months (mean, 11.9 months). All flaps had satisfactory appearance and texture, and no patients experienced limited hip and knee joint mobility from the donor site operation. CONCLUSIONS: Compound VL muscle and ALTP flaps are a reliable option to reconstruct complex defects of the extremities. Identifying three flap types allowed for more precise customization to cover complex defects with limited donor site morbidity.

A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia.

BACKGROUND: Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders. METHODS: The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction. RESULTS: We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM. CONCLUSIONS: A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.

A Design for the Dual Skin Paddle Circumflex Scapular Artery Perforator Flap for the Reconstruction of Complex Soft-Tissue Defects in Children: Anatomical Study and Clinical Applications.

BACKGROUND: The main drawbacks of the use of the circumflex scapular artery perforator (CSAP) flap for complex soft-tissue defect repair are the limitation of skin paddle size, which can be harvested to allow precise wound coverage and primary closure of the donor site. We developed a variant of the dual skin paddle CSAP flap to extend its applications and minimize donor-site morbidity when reconstructing complex soft-tissue defects in children. METHODS: A detailed anatomical investigation of circumflex scapular artery (CSA) branches was conducted using a standardized injection of lead oxide in 25 fresh cadavers. Dual skin paddle CSAP flaps were harvested for the reconstruction of complex defects in the extremities in 16 children. Three types of dual skin paddle CSAP flap were used in this study: transverse chain-shaped, oblique chain-shaped, and trefoil-shaped flaps. RESULTS: Three CSA branching patterns with superior branch diameters were observed: 34% of CSAs were of the transverse branch dominant type, 54% were of the descending branch dominant type, and 12% were of the codominant type. Sixteen dual skin paddle CSAP flaps were elevated successfully; they were of the transverse chain-shaped type in 2 cases, the oblique chain-shaped type in 9 cases, and the trefoil-shaped type in 5 cases. All flaps survived postoperatively. Primary closure of the donor site was achieved in all cases. CONCLUSIONS: The CSA system is an appropriate source for harvesting dual skin paddle CASP flap. Use of this flap for the reconstruction of complex soft-tissue defects in the extremities in children is an alternative approach that reduces morbidity and improves the cosmetic outcome at the donor site.

Reconstruction of Large Soft Tissue Defects of the Extremities in Children Using the Kiss Deep Inferior Epigastric Artery Perforator Flap to Achieve Primary Closure of Donor Site.

BACKGROUND: The closure of massive skin defects remains challenging, particularly in children. In this report, we describe a technique to achieve primary donor site closure using the kiss deep inferior epigastric perforator (DIEP) flap for the reconstruction of large soft tissue defects located in the extremities of children. METHODS: From May 2011 to May 2016, a retrospective analysis was conducted on 10 pediatric patients with extensive soft tissue defects and reconstruction with double-skin paddle DIEP flap. After harvesting the flap, the skin paddle was divided into 2 separate paddles with a common vascular supply, and then the 2 paddles were sutured side by side through translating 2 paddles or rotating one of the paddles by 90 or 180 degrees, effectively doubling the width of the flap and rejoining it at the recipient site. Data on patient age, medical history, defect size, flap dimensions, recipient vessels, donor site closure, complications, and follow-up were reviewed retrospectively. RESULTS: Nine children had major soft tissue defects of the lower limb, and the remaining one had an upper limb defect. Only 1 case was complicated by partial necrosis of 1 paddle. Primary donor site closure was accomplished in all cases. The flaps were well matched on texture and contour, except that the 2 flaps were bulky at postoperative follow-up. There was no donor site breakdown, with only a slightly noticeable linear scar. CONCLUSION: The kiss DIEP flap could be an alternative for reconstruction of large soft tissue defects of the extremities in children, with lower morbidity and improved cosmetic of the donor site.

Utilization of Microdissected Thin Perforator Flap Technique in the Treatment of Bulky and Deformed Skin Flaps.

BACKGROUND: This study investigates the feasibility and clinical impact of the microdissected thin perforator skin flap strategy on bulky and deformed skin flaps during second-stage revision surgery. METHODS: Seventeen patients were selected and underwent the microdissected thin perforator skin flap technique to treat bulky and deformed skin flaps after free flap reconstruction between October 2013 and October 2015. Perforator vessels were isolated and protected under a microscope. Subdermal fat with a thickness of 4 mm to 7 mm was preserved, and excess adipose tissue was resected. RESULTS: No skin flap necrosis was observed after the operation in all 17 patients, and all wounds healed without complications. Patients were followed up for 3 to 24 months, with an average follow-up time of 10 months. The skin flaps maintain normal color and texture. Both appearance and function of the recipient sites were improved significantly. CONCLUSIONS: The utilization of microdissected thin perforator flap technique to further thin bulky skin flaps at the second stage can be effective in a single operation. The blood supply of all free flaps was preserved, with no evidence of necrosis or healing complications. This technique offers an effective approach for secondary thinning of bulky free flaps.