Individualized design program of multiple flaps for adapting different zones to repair large irregular wounds in children.

Objective: Management of large irregular wounds in children had been confusing plastic and reconstructive surgeons. Herein, this study was aimed to propose a new treatment method based on the principle of adapting different recipient zones to overcome the intractable wounds, simplifying and programing the design process of targeted flaps for covering large irregular soft-tissue defects. Patients and methods: From January 2009 to December 2020, 31 children (9 girls and 22 boys) aged 3-16 years (mean 9.8 years) underwent multiple modular flaps with edge to edge splicing reconstruction of the lower extremities. All the wounds were large with non-adjacent defects and with or without a dead space. Several variants of flaps were harvested according to the needs and reconstruction requirements of patients. Results: A total of 71 flaps were harvested from 31 patients and all flaps donor sites received primary closure. Nine patients underwent split-thickness skin grafting, and three cases of flaps survived from vascular crisis by rebuilding the vessels and the rest accepting LD flap transplants. And five partial necrosis of the distal epidermis flaps recovered using skin grafting and dressing change. No major complication was encountered in other patients and donor sites, except one heel ulcer. During the follow-up (ranging from 16 to 38 months, mean 27.7 months), aesthetic and functional results of reconstructed limbs were satisfactory in all patients. Conclusions: The Individualized design program of multiple flaps for adapting different recipient zones is an alternative for repairing large irregular soft-tissue defects in children, beneficial for plastic and reconstructive surgeons to simplify and program the process of designing and perform multiple flaps to achieve this goal. Level of evidence: III, Retrospective.

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.

The versatile thoracodorsal artery perforator flap for extremity reconstruction: from simple to five types of advanced applications and clinical outcomes.

BACKGROUND: Application of the thoracodorsal artery perforator (TDAP) flap is known to be a popular and reliable method for extremity reconstruction. This manuscript presents our clinical outcomes in reconstructing soft tissue defects using simple and advanced TDAP flaps. METHODS: From 2013 to 2022, 53 patients with a mean age of 23 years (ranging from 2 to 72 years) underwent reconstructive surgery with different patterns of free TDAP flaps, including chimeric TDAP flaps, double skin paddle TDAP flaps, flow-through TDAP flaps, conjoined TDAP flaps, and microdissected debulking TDAP flaps. RESULTS: All TDAP flaps survived. The size of the TDAP skin paddle ranged between 5 × 3 and 25 × 10 cm2. Primary closure of the donor site was achieved in all patients in the simple application group, and one patient in the advanced application group underwent partial skin grafting. Partial flap loss occurred in one case in the simple TDAP flap group and four cases in the advanced application group. There was one case of flap bulkiness and two cases of scar hyperplasia in the simple TDAP flap group. The mean follow-up duration was 11 months (4-46 months). CONCLUSIONS: The free TDAP flap, with five types of advanced applications, makes it versatile for reconstructing different kinds of soft tissue defects of the extremities that can be used to achieve individualized defect reconstruction, minimize donor site morbidities, and an aesthetic appearance.

Variations in deep iliac circumflex artery perforator chimeric flap design for single-stage customized-reconstruction of composite bone and soft-tissue defect.

BACKGROUND: The deep iliac circumflex artery (DICA) perforator (DICAP) chimeric flap is a valuable treatment strategy for single-stage reconstruction of composite bone and soft-tissue defects in upper and lower extremities. However, its utilization rate remains low owing to anatomical variations that lead to challenges when identifying and dissecting perforators. METHODS: A comprehensive anatomical investigation was conducted on the DICA system by injecting lead oxide into 12 fresh cadavers following a standardized procedure. From January 2008 to December 2020, 30 patients with composite bone and soft-tissue defects received reconstruction surgery with DICAP chimeric flap. One of the four specified surgical techniques was used to create a modified DICAP chimeric flap for the patients based on the size, shape, and location of the defect. RESULTS: Two branching patterns of DICA, transverse and ascending branches, were observed, and the former gave off the osteomusculocutaneous perforators and terminal musculocutaneous perforators. Thirty DICAP chimeric flaps were elevated successfully. The size of the skin paddles measured from 9 × 4.5 cm to 22 × 9 cm, and the bone components ranged from 3 × 2.5 × 1.5 cm to 6 × 3.5 × 2 cm. All flaps survived successfully after the operation, and all patients achieved primary closure of the donor sites. No patient encountered the fracture of transferred iliac segments. The mean bone union time was 5.5 months (ranging from 4 to 8 months). CONCLUSION: The DICA system is a suitable source for harvesting the DICAP chimeric flap to reconstruct composite bone and soft-tissue defects. It provides a flexible design for individualized coverage of such defects with limited donor-site morbidity.

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.

Clinical application of magnetic resonance lymphangiography in the vascularized omental lymph nodes transfer with or without lymphaticovenous anastomosis for cancer-related lower extremity lymphedema.

Background: The recent increase in the number of patients with lower extremities lymphedema and the development of microsurgery techniques have led to a rise in lymphedema treatment. Vascularized omental lymph node transfer (VOLT), an emerging treatment modality for extremity lymphedema, has shown its unique advantages in reconstructing lymphatic circulation and absorbing exudated lymphatic fluid. Patients who underwent radical tumor resection with/without radiation therapy treatment often present with impairment or degeneration of the inguinal lymph nodes. For such cases, VOLT could provide adequate lymph nodes and tissue to absorb edema fluid in these areas. Therefore, we analyzed the operative outcomes of VOLT under the guidance of magnetic resonance lymphangiography (MRL) in this study, as this individualized and precise surgical procedure could benefit patients and improve their quality of life. Methods: From November 2021 to September 2022, a total of 14 patients' 19 legs with extremity lymphedema underwent a VOLT with or without lymphaticovenous anastomosis (LVA). Outcomes, including circumference reduction rates, preoperative and postoperative MRL results, and other complications, were analyzed. Results: The mean follow-up period was 8.86±1.41 months (range, 7-11 months). The mean circumference reduction rates {circumference reduction rate (%) = [1 - (postoperative affected limb - healthy limb)/(preoperative affected limb - healthy limb)] × 100%} of different planes (i.e., ankle, 10 cm above the knee, 10 cm below the knee, 10 cm above the ankle, and 20 cm above the knee) were 15.64%±40.08%, 11.79%±30.69%, 20.25%±24.94%, 7.73%±30.05%, -1.517%±16.75%. Notably, one patient had multi-drug-resistant gram-negative infections, which resulted in the loss of three flaps. The postoperative MRL showed improved lymphatic drainage and lower extremity volume in the remaining 13 cases. Conclusions: The precision evaluation of inguinal lymph nodes and lower extremities lymphatic system through MRL using VOLT can provide surgeons with a comprehensive understanding and reliable evidence for the treatment of cancer-related lower extremity lymphedema.

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.

Knowledge mapping and emerging trends of ferroptosis in ischemia reperfusion injury research: A bibliometric analysis (2013-2022).

Objective: Ischemia/reperfusion (I/R) injury is an inevitable dilemma when previously ischemic multiple organs and tissues are returned to a state of blood flow, with confirming a critical role of ferroptosis in molecular, pathway mechanisms, subcellular structure. Discovering the potential relationship may provide useful approaches for the clinical treatment and prognosis of the pathophysiological status of IRI. Therefore, a comprehensive visualization and scientometric analysis were conducted to systematically summarize and discuss the "ferroptosis in ischemia reperfusion injury" research to demonstrate directions for scholars in this field. Methods: We retrieved all publications focusing on I/R injury and ferroptosis from the Web of Science Core Collection (WoSCC), published from 2013 to October 2022. Next, scientometric analysis of different items was performed using various bibliometrics softwares to explore the annual trends, countries/regions, institutions, journals, authors and their multi-dimensional relationship pointing to current hotspots and future advancement in this field. Results: We included a total of 421 English articles in set timespan. The number of publications increased steadily annually. China produced the highest number of publications, followed by the United States. Most publications were from Central South University, followed by Sichuan University and Wuhan University. The most authoritative academic journal was Oxidative Medicine and Cellular Longevity. Cell occupied the first rank of co-cited journal list. Andreas Linkermann and Scott J Dixon may have the highest influence in this intersected field with the highest number of citations and co-cited references respectively. The essential biological reactions such as oxidative stress response, lipid peroxidation metabolism, anti-inflammmatory and pro-inflammatory procedure, and related molecular pathways were knowledge base and current hotspots. Molecules pathways exploration, effective inhibition of I/R injury and promising strategy of improving allografts may become future trends and focuses. Conclusions: Research on ferroptosis in I/R injury had aroused great interest recently. This first bibliometric study comprehensively analyzed the research landscape of ferroptosis and I/R injury, and also provided a reliable reference for related scholars to facilitate further advancement in this field.

Down-Regulation of HSP by Pd-Cu Nanozymes for NIR Light Triggered Mild-Temperature Photothermal Therapy Against Wound Bacterial Infection: In vitro and in vivo Assessments.

Purpose: We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial's heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy. Methods: We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs. Results: In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria's sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment. Conclusion: The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.

Itaconic acid induces angiogenesis and suppresses apoptosis via Nrf2/autophagy to prolong the survival of multi-territory perforator flaps.

Background: Perforator flaps are widely used in hand microsurgery to reconstruct and repair soft tissue injuries. However, ischemia and subsequent ischemia-reperfusion injury may cause distal necrosis of the flap. Itaconic acid (IA) is a modulator of macrophage function, which exerts anti-inflammatory effects in macrophage activation. Methods: The necrotic area of the flap was detected by measuring the flap temperature with an infrared thermometer. Flap cell apoptosis was detected by TUNEL staining and Western blot analysis of the apoptosis-associated proteins Bcl-2 and Bax. HE staining was used to detect angiogenesis of the skin flaps. CD31 was detected to identify positive vascular expression, and the survival of choke vessels in different areas of the skin flap was assessed by arteriography. In addition, Western blot was performed to quantify the expressions of VEGF, Nrf2, LC3II, SQSTM1, and CTSD. Results: Itaconic acid raises VEGF protein levels in skin flaps and the number of CD31-positive vessels. The skin flaps in the IA treatment group exhibited higher neovascularization and less necrosis than those in the control group. The results of TUNEL staining and Western blot revealed that Itaconic acid attenuated apoptosis in the ischemic area of flap. The combination of itaconic acid and Nrf2 inhibitor ML385 reversed this beneficial effect. The results revealed that itaconic acid attenuated apoptosis, enhanced angiogenesis, and enhanced autophagy. Conclusion: In summary, our findings indicate that itaconic acid might be an effective treatment to reduce flap necrosis. Additionally, this study identified a novel mechanism for the effects of itaconic acid on flap survival.

Substance P promote macrophage M2 polarization to attenuate secondary lymphedema by regulating NF-kB/NLRP3 signaling pathway.

Secondary lymphedema often occurs after filariasis, trauma, lymph node dissection and radiation therapy, which is manifested by infiltration of inflammatory cells and fibrosis formation in pathologically. Substance P is a widely used neuropeptide in the field of tissue repair, while the regenerative potential of the substance P has not been proven in the secondary lymphedema. In this study, animal model of secondary lymphedema was constructed by excising the skin and subcutaneous lymphatic network in the tail of mice, and the degree of swelling in the tail of mice was evaluated after 6 weeks under the treatment with substance P. Immunofluorescence staining was also performed to assess immune cell infiltration, subcutaneous fibrosis and lymphangiogenesis. The results revealed that substance P significantly alleviated post-surgical lymphedema in mice. Furthermore, we found that substance P promoted macrophages M2 polarization, a process associated with downregulation of the NF-kB/NLRP3 pathway. After application of disodium clodronate (macrophage scavenger, CLO), the positive effect of substance P in lymphedema is significantly inhibited. In vitro experiments, we further demonstrated the polarizing effect of substance P on bone marrow-derived macrophages (BMDMs), while substance P inhibited the activation of the NF-kB/NLRP3 pathway in BMDMs after the treatment of lipopolysaccharide (LPS). In addition, polarized macrophages were demonstrated to promote the proliferation, tube-forming and migratory functions of human lymphatic endothelial cells (hLEC). In conclusion, our study provides preliminary evidence that substance P alleviates secondary lymphedema by promoting macrophage M2 polarization, and this therapeutic effect may be associated with downregulation of the NF-kB/NLRP3 pathway.

Metformin induces M2 polarization via AMPK/PGC-1α/PPAR-γ pathway to improve peripheral nerve regeneration.

OBJECTIVES: Investigating the effect of metformin on peripheral nerve regeneration and the molecular mechanism. METHODS: In this study, a rat model of sciatic nerve injury and an inflammatory bone marrow-derived macrophage (BMDM) cell model were established. We assessed the sensory and motor function of the hind limbs four weeks after sciatic nerve injury, immunofluorescence was used to detect axonal regeneration and myelin formation, as well as local macrophage subtypes. We investigated the polarizing effect of metformin on inflammatory macrophages, and western blotting was applied to detect the molecular mechanisms behind it. RESULTS: Metformin treatment accelerated functional recovery, axon regeneration and remyelination, and promoted M2 macrophage polarization. In vivo, metformin transformed pro-inflammatory macrophages into pro-regeneration M2 macrophages. Protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), proliferator-activated receptor-γ co-activator 1α (PGC-1α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) increased upon metformin treatment. Moreover, inhibition of AMPK abolished the effects of metformin treatment on M2 polarization. CONCLUSION: Metformin promoted M2 macrophage polarization by activating the AMPK/PGC-1α/PPAR-γ signaling axis, thereby promoting peripheral nerve regeneration.

Efficacy comparison of vascularized iliac crest bone flap and Ilizarov bone transport in the treatment of traumatic bone defects of the tibia combined with large soft tissue defects.

BACKGROUND: Traumatic tibial defect complicated with soft tissue defect is a difficult problem in clinic. Vascularized iliac crest bone flap (VIBF) and Ilizarov bone transport are effective methods to treat tibial defects with limited defect length, which most need to be explored accordingly. METHODS: In this study, a total of 68 patients with traumatic tibial defect (ranging from 4 to 10 cm) and large soft tissue defect were collected retrospectively. The soft tissue defects were repaired by latissimus dorsal musculocutaneous flap (LD), anterolateral thigh flap (ALTF) or both. Thirty-three cases were treated with vascularized iliac crest bone flap transplantation and 35 cases were treated with Ilizarov bone transport. Intraoperative and postoperative follow-up data (including operation time, blood loss, bone union time, external fixation time, external fixation index, complication rate, reoperation rate, and functional evaluation) were recorded, and comparative analysis was performed. RESULTS: The median follow-up time was 32 months. Compared with Ilizarov group, the VIBF group exhibited statistically faster bone union time (6.3 ± 1.0 vs. 18.2 ± 3.0 months). Moreover, the VIBF group showed shorter EFT (7.3 ± 1.0 vs. 19.2 ± 3.0 months) and a better EFI (34.8 ± 9.2 vs. 84.2 ± 23.7 days/cm). The excellent and good rate of lower limb appearance evaluation in VIBP group was significantly better than that in Ilizarov group. The complication rate and reoperation rate were significantly higher in Ilizarov group. CONCLUSION: In summary, compared with Ilizarov bone transport, VIBP has the advantages of faster healing, shorter external fixation time, lower complication and reoperation rate, and better appearance within the limited defect length. Ilizarov bone transport is still preferred when the defect length exceeds the maximum repair length of the iliac flap. The daily handling required by bone transport process is painful. LEVEL OF EVIDENCE: III, Case-control study.

Individualized design of thoracodorsal artery perforator chimeric flap for customized reconstruction of complex three-dimensional defects in the extremities.

BACKGROUND: It was always challenging to accurately and effectively reconstruct the complicated defects with three-dimensional tissue deficits in the extremities. Muscle-chimeric perforator flap is an excellent choice for repairing those complicated wound. However, problems like donor-site morbidity and time-consuming intramuscular dissection still exist. This purpose of this study was to present a novel design of the thoracodorsal artery perforator (TDAP) chimeric flap for the customized reconstruction of complex three-dimensional tissue defects in the extremities. METHODS: From January 2012 to June 2020, 17 patients with complex three-dimensional deficits in the extremities were retrospectively analyzed. All patients in this series underwent extremity reconstruction using latissimus dorsi (LD)-chimeric TDAP flap. Three different types of LD-chimeric TDAP flaps were performed. RESULTS: A total of seventeen TDAP chimeric flaps were successfully harvested for the reconstruction of those complex three-dimensional defects in extremities. Among them, Design Type A flaps were used in 6 cases, Design Type B flaps were performed in 7 cases, and Design Type C flaps were used in the remaining 4 cases. The sizes of the skin paddles ranged from 6 cm × 3 cm to 24 cm × 11 cm. Meanwhile, the sizes of the muscle segments ranged from 3 cm × 4 cm to 33 cm × 4 cm. All the flaps survived. Nevertheless, one case required re-exploration owing to venous congestion. Moreover, the primary closure of the donor site was successfully achieved in all patients, and the mean follow-up time was 15.8 months. Most of the cases displayed satisfactory contour. CONCLUSION: The LD-chimeric TDAP flap is available for the reconstruction of complicated defects with three-dimensional tissue deficits in the extremities. It provided a flexible design for customized coverage of complex soft tissue defects with limited donor site morbidity.

Pedicled iliac bone flap grafting in the treatment of late presentation Legg-Calvé-Perthes disease.

Background: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis affecting children. The lack of effective and timely treatment results in severe sequelae in children (especially older ones). Although LCPD has been widely studied, little is known about its etiology. As a result, its clinical management is still challenging. This study will investigate the clinical and radiological results of patients older than 6 years and treated with pedicled iliac bone flap grafting for LCPD. Materials and methods: A total of 13 patients (13 hips) with late presentation of LCPD were treated with pedicled iliac bone flap grafting. Of the 13 patients, 11 were male and 2 were female. The average age of the patients was 8.4 years (range 6-13). Preoperational radiographs and pain scores were analyzed for lateral pillar classification and the Oucher scale. The final follow-up radiograph was classified using a modified Stulberg classification. Limping, extremity length inequality, and range of motion were clinically assessed. Results: The average follow-up of the patients was 70 months (range 46-120). During the surgery, seven hips were found to be lateral pillar grade B, two were grade B/C, and four were grade C. In the final examination, 12 hips were evaluated as good (Stulberg class I or II) and one as medium (Stulberg class III). There was limb shortening in one patient who was Stulberg class III. There was a significant difference between the preoperational and postoperational radiographic values and the Ocher scale, regardless of the surgical staging (P < 0.05). Conclusions: Pedicled iliac bone flap graft can treat LCPD accompanied by pain and lateral pillar stage B, B/C, and C in children over 6 years. Level of Evidence: Level IV-case series.

The research landscape on vascularized composite allografts: a bibliometric analysis (2002-2021).

OBJECTIVE: Vascularized composite allografts (VCAs) refer to the transplantation of multiple types of tissues during plastic and reconstructive surgery. Several publications have emerged in the field of VCA. However, there are no bibliometric studies on this topic. The aim was to multidimensionally analyze the knowledge base and hotspots in this subject. METHODS: We retrieved all publications related to VCA from the Web of Science Core Collection (WoSCC), published from 2002 to 2021. Next, scientometric analysis of different items was performed using various bibliometrics software to explore knowledge base, research hotspots, and advancement trends in this field. RESULTS: We included a total of 3,190 English articles from 2002 to 2021. The number of publications increased steadily annually. The United States produced the highest number of publications, followed by China. Most publications were from Harvard University, followed by Johns Hopkins University. The most authoritative academic journal was Plastic and Reconstructive Surgery. Transplantation occupied the first rank of co-cited journal list. Maria Z Siemionow may have the highest influence in the VCA field with the highest number of citations (n = 88) and co-cited references (n = 1252). Clinical studies on different allografts, immunosuppression, and tissue engineering were both the knowledge base and recent topics in VCA research. CONCLUSIONS: The first bibliometric study comprehensively summarized the trends and development of VCA research with steady growth over the past two decades. Currently, the most active topics are the clinical application of multiple allografts, immunosuppression strategies/therapies, and translation of tissue engineering to clinical practice.

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 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.

Comparison of retrograde anatomy iliac bone flap grafting versus anterograde anatomy iliac bone flap grafting for treatment of osteonecrosis of the femoral head.

BACKGROUND: Iliac bone flap with deep circumflex iliac artery is a common option in the treatment of Osteonecrosis of the femoral head (ONFH), and dissection of iliac bone flap is the key step for successful operation. This paper aims to introduce a new operative technique for dissecting iliac bone flap with deep circumflex iliac artery based on analysis of its advantages. METHODS: A total of 49 patients treated by retrograde anatomy and 52 patients treated by anterograde anatomy from January 2010 to December 2020 were recruited. The two groups were then compared in terms of the preoperative baseline conditions, intraoperative data, and postoperative Harris hip score (HHS). RESULTS: Compared with the retrograde anatomy group, the anterograde anatomy group had a significantly longer operating time, a significantly heavier intraoperative blood loss, a significantly higher rate of donor complication morbidity, a significantly higher rate of donor-recipient delayed healing, a significantly higher failure rate of iliac bone flap resection, a significantly higher rate of lateral femoral cutaneous nerve (LFCN) injury, and a significantly higher rate of ectopic ossification. No difference was found in postoperative HHS score between the two groups. CONCLUSION: As a new operative technique that can accurately locate the nutrient vessels of the iliac bone flap and quickly dissect the iliac bone flap with deep circumflex iliac artery while maintaining a comparable clinical effect, retrograde anatomy exhibited distinct advantages over anterograde anatomy in terms of simpler intraoperative operation, safer dissection, shorter operation time, lower blood loss, and fewer donor complications. LEVEL OF EVIDENCE: III, Retrospective.