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The clinical characteristics of malignant melanoma are highly variable between patient populations of different ethnicities. To explore the underlining genetic variations, we reviewed the clinical data of 242 malignant melanoma cases from Taiwan and among them submitted formalin-fixed paraffin-embedded tissue samples from 37 patients for whole-exome sequencing to identify the mutational signatures, tumor mutation burden and specific gene mutations. The genomic profiles and clinical outcomes were compared with the information derived from the publicly available TCGA and TGEN databases. Mutation signature 12 was the dominant signature in Taiwanese patients and represented approximately 45% of the mutation signatures observed. In contrast, mutation signature 7 was the most prominent among cases available in the TCGA database. Common gene mutations found in the TCGA melanoma dataset were not frequently found in melanomas from Taiwanese patients. There were a significant number of specific gene mutations that exclusively occurred in acral subtype but not in non-acral subtype melanomas, and vice versa. While certain common mutations form a shared core of genetic features, there appear to be specific genetic pathways that are involved in the occurrence of melanomas that grow in non-UV-exposed areas. Our findings have shed light on the tumorigenesis pathways involved in malignant melanoma.

Acute myocardial infarction (AMI) is a postoperative complication of major surgical procedures, including free flap surgery. It is the most common cause of postoperative morbidity and mortality. Moreover, patients receiving free flap reconstruction for the head and neck have significant risk factors such as coexisting coronary artery disease (CAD). Our primary aim was to ascertain predictors of perioperative AMI to enable early detection and consequently early treatment of perioperative AMI. Our secondary aim was to determine the group of patients who would be at a high risk for perioperative AMI after free flap surgery.This retrospective study enrolled patients who underwent free flap reconstruction surgery at the Division of Plastic and Reconstructive Surgery of Taipei Veterans General Hospital between 2013-01 and 2017-12.This study included 444 patients and 481 free flap head and neck reconstruction surgeries. Fifteen (3.1%) patients were diagnosed with perioperative AMI. Statistical analysis of the variables revealed that patients with underlying CAD or cerebrovascular accident (CVA) were at a high risk of developing perioperative AMI (odds ratio: 6.89 and 11.11, respectively). The flap failure rate was also higher in patients with perioperative AMI compared with those without perioperative AMI (P = 0.015).Patients with underlying diseases, such as CAD or CVA, constituted high-risk groups for perioperative AMI.

Direct-to-implant (DTI) breast reconstruction is one of the immediate implant-based breast reconstruction methods. If the amount of soft tissue (eg, muscle or fascia) is insufficient to completely cover the implant, biological scaffold or acellular dermal matrix can be safely used for implant coverage. In this study, we used an acellular porcine small intestinal submucosa (SIS) mesh (Biodesign; Cook Medical Inc, Bloomington, IN) for DTI reconstruction to explore the impact of its use on breast reconstruction results.We retrospectively assessed cases involving DTI reconstruction at Taipei Veterans General Hospital from 2015 to 2019. Women, 18 years or older, who underwent immediate DTI reconstruction after mastectomy were included in the study. Mastectomy may have been performed because of therapeutic or prophylactic reasons. Patients who did and did not use SIS mesh for reconstruction were studied separately, and the 2 groups were compared in terms of clinical outcomes and complications. The validated, self-administered BREAST-Q Reconstruction Module version 2.0 survey was used to evaluate health-related quality of life and satisfaction among patients who underwent breast reconstruction.A total of 30 DTI breast reconstructions were enrolled. The mean age was 49.2 years, and the mean body mass index was 22.3 kg/m2. The mean postoperative follow-up duration was 17.1 months. Nipple-sparing mastectomy was performed for 26 cases (86.7%), and DTI breast reconstructions using SIS mesh for implant coverage were done in 14 cases (46.7%). The overall complication rate was 53.3% in 30 reconstructions, with nipple complications being the most common complication. The non-SIS and SIS-using groups had a similar overall complication rate postoperatively. As for the quality-of-life assessment, the SIS group obtained a higher score on BREAST-Q than those for whom SIS was not used.Porcine SIS mesh might be a safe and effective alternative to biological scaffolds in immediate 1-stage implant-based breast reconstruction to improve the quality of life after surgery.

Sentinel lymph node (SLN) status is the predominant prognostic factor in patients diagnosed with clinically localized melanoma. The significance of completion lymph node dissection in patients with SLN metastasis is debatable. Not many studies have been conducted on acrallentiginous melanoma (ALM). This study aimed to characterize the prognostic factors of nodal positive ALM and confirm whether ALM patients can undergo the same treatment strategy as non-ALM patients in the Asian population.This is a retrospective review of patients who underwent surgery for cutaneous melanoma (CM) at Taipei Veterans General Hospital between January 1993 and December 2019. We investigated the risk factors for lymph node status. The association between clinicopathological factors and lymph node status of ALM and non-ALM patients was analyzed. Outcomes of completion lymph node dissection (CLND) performed following sentinel lymph node biopsy (SLNB) in the CM and ALM groups were compared.A total of 197 patients were included in this study. ALM was the most common histological subtype, accounting for 66.5% of all the cases. Patients in the CM and ALM subgroups with metastatic SLN ( p = 0.012) or lymph nodes ( p0.001 and p = 0.001) exhibited higher mortality rate. Multivariate analysis showed that patients with clinical presentation of T4 category tumor ( p = 0.012) and lymphovascular invasion ( p = 0.012) had a significantly higher risk of positive lymph nodes. The overall survival of patients with lymph nodes metastasis was not associated with the performance of CLND.Patients in the CM or ALM subgroups with metastatic SLNs or lymph nodes exhibited significantly poorer overall survival. Advanced Breslow thickness and lymphovascular invasion were independent predictive factors for CM and ALM patients with positive lymph node status. There was no significant difference in survival between CM and ALM patients following SLNB, regardless of CLND being performed.

Purpose Four hundred and ninety-nine patients had burn injuries in an explosion in Taiwan on June 27, 2015, 24 were admitted to the intensive care units of Taipei Veterans General Hospital. This study details our experience with surgical management of these patients, focusing primarily on various skin graft techniques. Materials and methods This single-center retrospective study included patients who underwent at least one of the previously mentioned skin graft techniques because of extensive skin defects. The demography, burn diagram, treatment modalities, postoperative outcome, and costs were all analyzed, and a comparison with traditional mesh skin grafts was performed. The literature was also reviewed. Results Fourteen patients underwent the Meek skin graft technique. Only 3 received ReCell and 1 cultured epithelial autograft (CEA) at separate time point. Overall, the autologous skin grafts, including Meek/ReCell/CEA were completed within 6 months. The average skin graft success rate was approximately 72.9%, 79.2%, and 38% in Meek, ReCell, and CEA, respectively. The infection rate was approximately 35.7%, 25%, and 100% in Meek, ReCell, and CEA, respectively. The average surgical cost and total medical cost were significantly higher in patients who underwent Meek/ReCell/CEA treatments. Conclusions In our experience, Meek and ReCell treatments had acceptable success rates, but CEA treatment not. ReCell and CEA treatments are useful in the event of extremely limited donor sites, and they are fragile, easily infected, and technically challenging. These techniques also require longer hospitalization and tend to be more expensive, all factors that should be considered when assessing treatment options.

Background The pandemic of SARS-CoV-2 (COVID-19), which began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries. Methods To facilitate emergent surgical interventions for these patients, we have reviewed the current literature and established an algorithm of precautions to be taken by operating room team members during the COVID-19 pandemic. Results The initial algorithm of preparation for surgical intervention during the COVID-19 pandemic was relatively simple. However, the abrupt increase of confirmed COVID-19 cases due to returned overseas travelers since mid-March 2020 disrupted the routine hospital clinical service. Due to the large number of febrile patients, the algorithm was therefore revised according to travel history, occupation, contact and cluster history (TOCC), unexplained fever/symptoms, and emergent/nonemergent surgery. TOCC (+) patients presenting with otherwise unexplained fever/symptoms would be regarded as belonging to the fifth category of "severe special infectious pneumonia." If the patient requires emergent surgery to relieve the non-life-threatening disorders, two times of negative COVID-19 tests are necessary before the operation is approved. For life-threatening situations without two negative results of COVID-19 tests, the operation schedule should be approved by the Chairman of Surgery Management Committee. Conclusion The application of a clear and integrated algorithm for operating room team members aids in effective personal protective equipment facilitation to keep both healthcare providers and patients safe as well as to prevent hospital-based transmission of COVID-19.

Using barbed thread lifting for facial rejuvenation has become popular these days due to its minimally invasive procedures with reduced complications. However, only limited studies regarding its mechanical properties for face suspension were published. The aim of this study was to evaluate suture-holding ability regarding its facelift property, and different specimens were tested in order to establish an in vitro model. Fresh porcine tissue and the synthetic material polydimethylsiloxane (PDMS) were selected to simulate human skin for evaluating barbed suture pull-out strength by the universal material testing machine. The results showed that the pull-out strength of barbs between different porcine tissues varied without consistency. By contrast, PDMS (30:1) showed more consistent pull-out strength in each testing, and the average maximum load force was close to porcine tissue. Furthermore, after submerging barbed sutures in PBS for 0 days (T0), 7 days (T7) and 14 days (T14), a trend of decreased average maximum load force, displacement and force of 1.5 mm/2 mm/3 mm displacement could be detected by in vitro testing with PDMS (30:1). These results provide support for using PDMS (30:1) to evaluate suture pull-out strength and holding/lifting capacities in vitro to obtain consistent and objective information for evaluating substantial equivalence of devices. The established in vitro method could be used for the future development of barbed thread lifting technology.

Severely burned patients are at high risk for cardiopulmonary failure. Promising studies have stimulated interest in using extracorporeal membrane oxygenation as a potential therapy for burn patients with refractory cardiac and/or respiratory failure. However, the findings from previous studies vary.In this study, the authors conducted a systematic review and meta-analysis using standardized mortality ratios to elucidate the benefits associated with the use of extracorporeal membrane oxygenation in patients with burn and/or inhalation injuries. A literature search was performed, and clinical outcomes in the selected studies were compared.The meta-analysis found that the observed mortality was significantly higher than the predicted mortality in patients receiving extracorporeal membrane oxygenation (standardized mortality ratio, 2.07; 95 percent CI, 1.04 to 4.14). However, the subgroup of burn patients with inhalation injuries had lower mortality rates compared to their predicted mortality rates (standardized mortality ratio, 0.95; 95 percent CI, 0.52 to 1.73). Other subgroup analyses reported no benefits from extracorporeal membrane oxygenation; however, these results were not statistically significant. Interestingly, the pooled standardized mortality ratio values decreased as the selected patients' revised Baux scores increased (R = -0.92), indicating that the potential benefits from the treatment increased as the severity of patients with burns increased.The authors' meta-analysis revealed that burn patients receiving extracorporeal membrane oxygenation treatment were at a higher risk of death. However, select patients, including those with inhalation injuries and those with revised Baux scores over 90, would benefit from the treatment. The authors suggest that burn patients with inhalation injuries or with revised Baux scores exceeding 90 should be considered for the treatment and early transfer to an extracorporeal membrane oxygenation center.

Background To surgically remove osteoma and to keep an optimal cosmetic profile would be very challenging. To solve the difficulty, we utilized the three-dimensional (3D) printing technologies in generating a patient-specific instrument guide (PSIG) for the safe removal of a skull bone tumor. Methods The preoperational brain computed tomography (CT) provided the digital imaging with thin slices, and then images were reconstructed into a 3D skull model. Based on the model, we designed a PSIG to make landmarks on the osteoma to avoid excessive removal of the skull bone. During the operation, the surgeons could remove the osteoma piece by piece by using the landmark as a reference point. Results The PSIG was successfully applied to remove an osteoma that measured 60 × 48 × 40 mm over the left frontoparietal skull of a female patient. The 3D CT reconstruction taken both before and 4 months after surgery showed a significant change in the appearance of the osteoma. Conclusion The PSIG was able to guide the surgeon in the safe removal of the skull osteoma, as well as in maintaining the cosmetic skull profile.

BACKGROUND Burns that affect ≥20% of the total body surface area (TBSA) trigger a major inflammatory response in addition to capillary leakage and loss of serum proteins including albumin. Persistent hypoalbuminemia is therefore common in major burn patients. The purpose of this study was to determine whether human albumin solutions can benefit major burn patients with persistent hypoalbuminemia. METHODS We conducted a retrospective review of major burn patients with ≥20% of TBSA involved at Taipei Veterans General Hospital between January 2007 and December 2018. Thirty-eight patients were enrolled. Patient demographics, burn characteristics, fluid balance, laboratory results, and outcomes were recorded through chart review. RESULT No significant differences were found in the baseline characteristics of patients who received

Background Merkel cell carcinoma (MCC) is rare among Asians. To evaluate the presence and characteristics of MCC in Taiwan, we described the characteristics, treatment, and prognostic findings of MCC in our institution. Methods We revisited and carried out a retrospective chart review of 16 consecutive patients with MCC treated from 1995 to 2018. Patient demographic data, tumor size, location, previous treatment, and follow-up data about presence of locoregional recurrence and metastasis were evaluated. Results There were 14 male and 2 female patients (mean age = 75.1 years; range = 26-91 years). Clinical follow-up revealed local recurrences in 5 patients 1 to 4 months after surgical excision. Lymph node metastasis was observed in 3 patients. We reviewed previously published articles and analyzed the clinical findings, pathologic examinations, and treatments. Conclusions Surgical wide excision of the primary tumor remains the mainstay of treatment for patients with local/regional MCC. Additional management strategies, such as lymphadenectomy, radiotherapy, chemotherapy, and targeted therapy, depend on the presence or absence of clinically detectable lymph node disease. The prognosis for MCC is variable. Our findings highlight the importance of maintaining a high clinical suspicion for this malignancy in the appropriate clinical context to avoid delays in diagnosis and management.

To present the complications of free-flap phalloplasty in three-staged female-to-male transgender surgery.This retrospective study included patients who underwent a three-staged free-flap phalloplasty for female-to-male transgender surgery between January 1988 and December 2013. Data regarding demographics, operative techniques, and complications were collected and analyzed.A total of 101 patients with a mean age of 30.2 years were included. Phalloplasty with traditional free forearm tube-in-tube fasciocutaneous flap was performed in 25 (24.8%) patients, free forearm fasciocutaneous flap with vaginal mucosa for a prefabricated urethra in 30 (29.7%) patients, free radial forearm osteocutaneous flap with vaginal mucosa for a prefabricated urethra in 22 (21.8%) patients, and free fibula osteocutaneous flap with vaginal mucosa for a prefabricated urethra in 24 (23.8%) patients. Complication rates of partial flap loss, urethrocutaneous fistula, urethral stricture, and hair or stone formation were 12.9%, 49.5%, 24.8%, and 5.0%, respectively. Patients receiving fibula osteocutaneous flap phalloplasty had the lowest overall complication rate (33.3%), followed by those with radial forearm osteocutaneous flap (40.9%), forearm fasciocutaneous flap (43.3%), and forearm tube-in-tube fasciocutaneous flap (80.0%). Forearm tube-in-tube fasciocutaneous flap procedure was associated with significantly higher rates of overall complications (p = 0.05), urethrocutaneous fistula (p = 0.005), and hair or stone formation (p = 0.002) compared with the other three types of procedures. Rates of all complications did not significantly differ among fibula osteocutaneous flap, radial forearm osteocutaneous flap, and forearm fasciocutaneous flap procedures.In free-flap phalloplasty for female-to-male transgender surgery, utilization of free fibula osteocutaneous flap with vaginal mucosa for a prefabricated urethra resulted in the lowest complication rate. Further comparisons among different procedures of phalloplasty are warranted.

Application of 3-dimensional (3D) printing technology has grown in the medical field over the past 2 decades. In managing orbital blowout fractures, 3D printed models can be used as intraoperative navigators and could shorten the operational time by facilitating prebending or shaping of the mesh preoperatively. However, a comparison of the accuracy of computed tomography (CT) images and printed 3D models is lacking.This is a single-center retrospective study. Patients with unilateral orbital blowout fracture and signed up for customized 3D printing model were included. Reference points for the 2D distance were defined (intersupraorbital notch distance, transverse horizontal, sagittal vertical, and anteroposterior axes for orbital cavity) and measured directly on 3D printing models and on corresponding CT images. The difference and correlation analysis were conducted.In total, 9 patients were reviewed from June 2017 to December 2020. The mean difference in the intersupraorbital notch measurement between the 2 modules was -0.14 mm (P = 0.67). The mean difference in the distance measured from the modules in the horizontal, vertical, and anteroposterior axes of the traumatic orbits was 0.06 mm (P = 0.85), -0.23 mm (P = 0.47), and 0.51 mm (P = 0.32), whereas that of the unaffected orbits was 0.16 mm (P = 0.44), 0.34 mm (P = 0.24), and 0.1 mm (P = 0.88), respectively. Although 2D parameter differences (1 mm) between 3D printing models and CT images were discovered, they were not statistically significant.Three-dimensional printing models showed high identity and correlation to CT image. Therefore, personalized models might be a reliable tool of virtual surgery or as a guide in realistic surgical scenarios for orbital blowout fractures.

Double-eyelid blepharoplasty is the most popular cosmetic surgery in Taiwan. The creation of a small palpebral fold along with reduction of eyelid fullness makes the eye look slightly larger, thereby leading to an appearance of youthfulness, alertness, and vitality. Herein, we propose a method of combining the techniques of arcade buried suture and forceps, which is designed to create a more physiologically natural double eyelid.We conducted a retrospective review of 45 patients who underwent double-eyelid surgery between December 2015 and December 2019. The procedures were performed by one senior surgeon using arcade suture upper blepharoplasty combined with the forceps technique. The patients' age ranged from 18 to 38 years (mean, 28 years). Ninety-one percent of the patients were women and were undergoing surgery for cosmetic reasons.Of the 45 patients who underwent arcade suture upper blepharoplasty with the forceps technique, no patients developed stitch abscess or granuloma, obvious asymmetry, disappearance of line, chemosis, and corneal injury. The follow-up period ranged from 3 months to 4 years (mean, 32 months). Patient satisfaction was very high.The arcade suture upper blepharoplasty combined with the forceps technique is a simple method for establishing a durable double eyelid without serious complication and providing excellent results.

Fresh fat grafts are commonly used in both esthetic and reconstructive surgeries, but the graft resorption rate varies. Cryopreservation of unused fat for later touch-up is one option to resolve this variation. In our previous studies, we found that fat cryopreservation may be a practical strategy for storing fat tissue. To explore the cryopreservation method, we evaluated the role of vascular endothelial growth factor (VEGF) in human frozen fat grafts.The concentration of VEGF in human frozen fat grafts subjected to different preservation times was determined using Western blotting and enzyme-linked immunosorbent assay. The angiogenic effect of frozen fat grafts was evaluated using a chorioallantoic membrane assay. Furthermore, the impact of adding human adipose-derived stem cells (hADSCs) or different concentrations of avastin (bevacizumab) to frozen fat grafts on angiogenesis was assessed. The viability of frozen fat grafts with or without hADSCs was evaluated using a nude mouse implantation study. Explanted fat tissues were examined on days 1, 4, 7, 14, 28, and 90, and morphological and histological analyses, immunohistochemistry, and enzyme-linked immunosorbent assay (VEGF concentration) were carried out.No significant difference in VEGF concentration between fresh and frozen fat was observed with respect to preservation duration. In the chorioallantoic membrane assay, frozen fat grafts with hADSCs displayed significantly enhanced angiogenesis. Avastin was found to decrease angiogenesis in frozen fat grafts. However, in the nude mouse implantation study, frozen fat grafts displayed VEGF maintenance, with the highest concentration observed on day 7. Adding hADSCs to the graft further increased the VEGF concentration and CD31 expression. Fat graft viability was found to be higher in the frozen fat grafts containing hADSCs than in grafts without hADSCs.Human fat grafts can maintain VEGF expression under frozen conditions for at least 12 months. The addition of hADSCs to the frozen fat graft could further enhance angiogenesis, VEGF expression, and fat cell viability.

Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery.This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed.The results showed that the early recovery group had a shorter duration of sedation (P0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation.Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.

The use of cryopreserved allogenic vascular graft in reconstructive microsurgery has rarely been reported. Here, we report a case of lower extremity reconstruction using cryopreserved hepatic artery as the vein conduit. Postoperative flap perfusion was uneventful with satisfactory wound healing, and graft patency was observed on follow-up color Doppler. Thus, cryopreserved allogenic vascular graft could be a source of vascular conduit in microsurgery.

Background The goal of this study was to investigate the prognostic factors for locoregional recurrence and metastasis in patients with cutaneous melanoma (CM) who underwent surgery, especially in the acral lentiginous melanoma (ALM) subtype. Methods This study was a retrospective review of patients who underwent surgery for CM at Taipei Veterans General Hospital between 2000 and 2018. We investigated the risk factors for locoregional and distant metastases. The association between clinicopathological factors and locoregional recurrence and distant metastasis of the CM and ALM subtypes was analyzed. In addition, the outcomes between the ALM and non-ALM groups were compared. Results A total of 161 patients were included in the analysis. The most common histological subtype was ALM. The overall locoregional recurrence rate of CM was 13.0% and the distant metastasis rate was 42.9%, whereas that of the ALM subtype was 12.5% and 45.5%, respectively. In patients with CM, male sex, tumor with lymphovascular invasion, and positive lymph node status were the prognostic factors for both locoregional recurrence and distant metastasis. Among the patients with ALM, positive lymph node status was significantly associated with both locoregional recurrence and distant metastasis. Conclusion In this cohort, factors influencing locoregional recurrence and distant metastasis were similar between the ALM and non-ALM groups. The above-recommended surgical margin did not show any benefit in either the CM or the ALM subtype. ALM can be handled using the same surgical strategy as CM in the Asian population.

Decellularized vascular grafts are useful for the construction of biological small-diameter tissue-engineered vascular grafts (≤6 mm). Traditional chemical decellularization requires a long treatment time, which may damage the structure and alter the mechanical properties. Decellularization using sonication is expected to solve this problem. The aim of this study was to develop an effective decellularization method using ultrasound followed by washing. Different power values of sonication at 40 kHz were tested for 2, 4, and 8 h followed by a washing procedure. The efficacy of sonication of decellularized human umbilical artery (sDHUA) was evaluated via DNA content, histological staining, mechanical properties, and biocompatibility. The sDHUAs were further implanted into rats for up to 90 days and magnetic resonance angiography (MRA) was performed for the implanted grafts. The results demonstrated that treatment of human umbilical artery (HUA) by sonication at ultrasonic power of 204 W for 4 h followed by washing for 24 h in 2% SDS buffer could eliminate more than 90% of cells and retain similar mechanical properties of the HUA. Recellularization was assessed by scanning electron microscopy (SEM), which indicated that sDHUA provided niches for human umbilical vein endothelial cells (HUVECs) to reside, indicating in vitro cytocompatibility. Further implantation tests also indicated the fitness of the sonication-treated HUA as a scaffold for small-caliber tissue engineering vascular grafts.

Matrix metalloproteinase 9 (MMP-9) expression is upregulated in vascular inflammation and participates in vascular remodeling, including aneurysm dilatation and arterial neointima development. Neointima at the arteriovenous (AV) fistula anastomosis site primarily causes AV fistula stenosis and failure, however, the effects of MMP-9 on perioperative AV fistula remodeling remain unknown. Therefore, we created AV fistulas (end-to-side anastomosis) in wild-type (WT) and MMP-9 knockout mice with chronic kidney disease to further clarify this. Neointima progressively developed in the AV fistula venous segment of WT mice during the four-week postoperative course, and MMP-9 knockout increased the lumen area and attenuated neointima size by reducing smooth muscle cell and collagen components. Early perioperative AV fistula mRNA sequencing data revealed that inflammation-related gene sets were negatively enriched in AV fistula of MMP-9 knockout mice compared to that in WT mice. qPCR results also showed that inflammatory genes, including tumor necrosis factor-a (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were downregulated. In addition, Western blot results showed that MMP-9 knockout reduced CD44 and RAC-alpha serine/threonine-protein kinase (Akt) and extracellular signal-regulated kinases (ERK) phosphorylation. In vitro, MMP-9 addition enhanced IL-6 and MCP-1 expression in vascular smooth muscle cells, as well as cell migration, which was reversed by an MMP-9 inhibitor. In conclusion, MMP-9 knockout attenuated AV fistula stenosis by reducing perioperative vascular inflammation.

Background Severely burned patients, particularly when compounded with inhalation injuries, are at high risk for cardiopulmonary failure. Recently, promising studies have stimulated interest in using extracorporeal membrane oxygenation (ECMO) as a potential therapy for burn patients with refractory cardiac and/or respiratory failure. Several observational studies have been reported, but the findings in these vary. Methods In this study, we conducted a systematic review and meta-analysis using standardized mortality ratios (SMRs) to elucidate the benefits associated with the use of ECMO in patients with burn and/or inhalation injuries. A literature search using PubMed, EMBASE, MEDLINE, and the Cochrane Library were performed from inception to October 20, 2020. Clinical outcomes in the selected studies were compared. Results 22 studies were included in the final review and analysis. 13 studies with a total of 75 patients were included in SMR quantitative analysis. The overall pooled mortality rate of burn patients receiving ECMO was 48%. The meta-analysis found that the observed mortality was significantly higher than the predicted mortality in patients receiving ECMO, with a pooled SMR of 2.07 (95% CI: 1.04–4.14). However, in the subgroup of burn patients with inhalation injuries, all patients receiving V-V ECMO had lower mortality rates compared to their predicted mortality rates, with a pooled SMR of 0.95 (95% CI: 0.52–1.73). Other subgroup analyses, including an adult group, pediatric group, V-V setting group, and a V-A setting group reported no benefits from ECMO; however, these results were not statistically significant. Interestingly, the pooled SMR values decreased as the selected patients’ revised Baux scores increased (R=-0.92), indicating that the potential benefits from the ECMO treatment increased as the severity of patients with burns increased, especially when the patients’ revised Baux scores exceeded 90. Conclusions Our meta-analysis revealed that burn patients receiving ECMO treatment were at a higher risk of death. However, select patients, including those with inhalation injuries and those with the revised Baux scores over 90, would benefit from ECMO treatment. We suggest that burn patients with inhalation injuries or with revised Baux scores exceeding 90 should be considered for ECMO treatment and early transfer to an ECMO centre.

Preventive effects of two traditional Chinese medicines, Chia-wei-hsiao-yao-san and Kuei-lu-erh-hsien-chiao, on the bone loss induced by ovariectomy in Long-Evans rats were investigated. The rats were divided randomly into five groups. The first group was given a sham operation with administration of distilled water, whereas the second, third and fourth groups were ovariectomized with administration of distilled water, Kuei-lu-erh-hsien-chiao and Chia-wei-hsiao-yao-san, respectively. The rats of the fifth group were embedded by intraperitoneal with a silicon tube containing 17 β-estradiol (10% in cholesterol) at a dose of 10μg/kg. Eight weeks later, the mean differences of spinal bone mineral density (BMD) in groups 1, 4 and 5 were significantly higher than that in group 2. The mean differences of plasma alkaline phosphatase (ALP) in groups 1 and 5 were significantly lower than those in group 2, but there were no significant differences between groups 1 and 5. In histologic analysis, the cross sections from lower third of the tibial shaft in group 3 showed more mucopolysaccharide accumulation than those in groups 4 and 5. The urinary N-telopeptide of type I collagen (NTx) levels did not differ significantly among groups 1, 2, 3, 4 and 5. Nevertheless, the mean differences of urinary deoxypyridinoline (Dpd) levels in group 5 were significantly higher than those in group 2. 17 β-estradiol and Chia-wei-hsiao-yao-san showed inure profound effect than Kuei-lu-erh-hsien-chiao in the prevention of bone loss in the ovariectomized (OVX) rats. Although 17 β-estradiol exerted more profound effect, Chia-wei-hsiao-yao-san showed good compliance and safety for relief of climacteric symptoms for postmenopausal women in a previous study. Therefore, Chia-wei-hsiao-yao-san might be an alternative for preventing bone loss.

Glutathione is ubiquitous in eucaryotic cells and is implicated in many cellular functions. Release of reduced and oxidized glutathione (GSH and GSSG) into the plasma and the ratio of GSH/GSSG are considered a reliable index to evaluate the status of oxidative stress in biological systems. As storage temperatures and time periods have not been studied and discussed, we evaluated the effects of storage period and temperatures on the stability of GSH in blood samples by an automated capillary electropherograph system. After two-way ANOVA analysis, the result indicated that there were statistical significance between the GSH status and the storage period, and the GSH status and the preserved temperature as well. However, there was no statistical significance between samples with EDIA or with EDTA-NaF added as anticoagulant. Furthermore, no matter which freezing temperature (-20℃ or -80℃) was used for storing the samples, the concentration of total GSH was quite consistent over the course of the study. We suggest that the alteration of the GSH status at room temperature should be due to not only the autoxidation of GSH but also the enzyme-catalyzed degradation of GSH and GSSG.

Background Extracorporeal membrane oxygenation (ECMO) has been reported to improve outcomes in patients with refractory respiratory failure. These successful experiences have stimulated interest in using ECMO as a potential therapy for patients with acute pulmonary failure resulting from burn and inhalation lung injury. Current literature has supported the use of ECMO in critically-ill, pediatric burn patients. On the other hand, it is controversial to apply ECMO in adult burn patients, and the evidence is limited by the shortcomings of small sample size. We share our successful experience of ECMO treatment in the casualties of the Formosa Water Park Dust Explosion Disaster. Methods We investigated the data from the dust explosion event, which happened on June 27, 2015, in New Taipei, Taiwan. The medical records of five patients with severe acute respiratory distress syndrome receiving ECMO were evaluated. Results The mean study subject age was 21.8 years, with a mean total body surface area burned of 82.9%. The average time to ECMO setup was 48.6 days. Survivors and non-survivors averaged four days and 77.7 days, respectively. The overall mortality rate was 40%. Three survivors were discharged without any ECMO-related complications or pulmonary sequelae after one year of follow up. Conclusions ECMO may be a lifesaving modality for burn patients with severe lung injury who are nonresponsive to maximal medical management, especially for young patients with early ECMO intervention.

Background: Autologous fat graft is a well established technique for soft tissue augmentation and the most significant drawback remains the unpredictability of the absorption rate and the possible repeating fat harvest procedures. In our basic study, we found evidence to support that fat cryopreservation is a practical method of storing fat tissue and several anecdotal clinical experiences suggest its clinical efficacy. Methods: Thirty two patients who received autologous cryopreserved fat grafts for facial deficiencies were retrospectively reviewed. Autologous cryopreserved fat grafts were transplanted for “touch up” or augmentation of other soft tissue deficiencies at least three months after fresh fat grafting, The patients' satisfaction was evaluated by a study-specific questionnaire. Results: 84 autologous fresh fat graft and 178 autologous cryopreserved fat graft procedures for the face were performed in 32 patients. There was no infection, skin retraction, fibrosis or necrosis identified except one patient complained of lump formation in the left upper lid (1/178, 0.6%). The self-assessment questionaaire revealed no statistical difference of effectiveness rating between the fresh and cryopreserved fat grafting results (mean± standard deviation: 8.64±1.09 vs 8.73±0.985; P > 0.05) but there was significant statistical difference of convenience rating between the fresh and cryopreserved fat grafting (mean± standard deviation: 2.68±1.07 vs 8.41±1.05; P < 0.05). Of the twenty-two patients who returned the questionnaire, all reported willing to have the treatment in the future (9.73±0.456) and all said that they would like to recommend this treatment to their friends (9.82±0.395). Conclusions: Autologous cryopreserved fat graft is a safe, simple, and convenient technique to restore facial soft tissue defects with acceptable patient satisfaction rate. Clinical Question/Level of Evidence: Therapeutic, IV.

Corneal inflammation and injury result in scarring and the loss of transparency of the cornea, accounting for a million cases of blindness worldwide each year. Hence, tissue engineering for the reconstruction of the corneal endothelium is a potential therapy. In this study, hydrogels composed of various ratios of hyaluronic acid (H) and Pluronic F-127 (F) were synthesized. These hydrogels can transit between liquid below 15 °C and hydrogel at 37 °C and were injectable for treating corneal wounds via in situ polymerization. The hydrogel preparations were assessed by Fourier transform infrared spectroscopy and scanning electron microscopy, and their physical–chemical properties, including transparency, viscoelastic properties, biodegradation and swelling properties, were also evaluated. The results demonstrated that the two ratios of hydrogels, H:F = 1:15 (H1F15) and 1:20 (H1F20), exhibited thermal responsive rheological properties, biodegradation and swelling properties. Specially, the H1F15 hydrogel incubated with 10,000 U of a lysozyme solution still retained over 70% of its remaining weight for 7 days. Moreover, this study further compared the characteristics of bovine corneal endothelial cells (BCECs) cultured on the hydrogels with and without porcine platelet rich plasma (P-PRP) using cytotoxicity, migration, apoptosis/necrosis and cell cycle assays. The results showed that the H1F15 hydrogel with P-PRP displayed higher cell viability and cell migration. In addition, the incorporation of P-PRP positively affected the hydrogel to reduce apoptosis and to enhance the cell cycle of BCECs. Taken together, these results confirmed that the H1F15 hydrogel lacks cytotoxicity and is biodegradable. BCECs can survive, grow and retain normal characteristics in the H1F15 hydrogel with P-PRP. These results provide an opportunity for corneal endothelium reconstruction using a tissue engineering approach with the H1F15 hydrogel with P-PRP.

Ear reconstruction remains a challenge for plastic surgeons. A tissue-engineering approach could provide another route for obtaining shape maintenance in neoauricular tissue.The authors designed a novel tissue-engineering auricular construct by culturing human adipose stem cells, which differentiated into osteocytes but not chondrocytes, in small intestine submucosa scaffolds. The authors evaluated cell growth potential and mechanical properties. An ear-shaped construct was created in vitro and then implanted in the backs of nude mice. The histology, cellularity, neovascularization, mechanical properties, and ear shape maintenance were investigated.In vitro, human adipose stem cells could be successfully seeded in the small intestine submucosa and differentiated toward osteogenesis. The ear-shaped human adipose stem cell/small intestine submucosa construct could maintain its shape in vivo up to 1 year. Alizarin Red S staining confirmed osteogenic differentiation. CD31 stain showed prominent angiogenesis in the human adipose stem cell/small intestine submucosa construct at 6 months and persistence up to 1 year. h-MHC stain revealed the maintenance of cellularity at 6 months and persistence up to 1 year. The mechanical properties were similar to those of native ear cartilage.The authors' study found that the combination of human adipose stem cells and small intestine submucosa could provide a more durable ear-shaped construct in vivo. The mechanical properties, shape, and cellularity were maintained in the constructs for up to 12 months.Therapeutic, V.

Background Split-thickness skin grafts are widely used in reconstruction of large area defects. Conventional postoperative recipient site care includes saline-moistened gauze with a protective layer of petroleum gauze and splints for immobilization. This method causes pain while changing the dressing. We designed a better occlusive drainage system for split-thickness skin grafts. We compared the treatment effect and subjective evaluation of our occlusive drainage system with that of the conventional method for coverage of split-thickness skin grafts. Methods A randomized controlled trial was carried out in patients who received split-thickness skin grafts. Patients aged 24–76 years were randomly assigned to the occlusive drainage system or the conventional indirect wet dressing method. The status of graft take, pain, and subjective evaluations were compared. Results Twenty-eight participants were enrolled, with 14 in each group. The percentage of graft take was no difference between the 2 groups. No wound infection developed. Patients in the occlusive drainage system group experienced less pain and greater satisfaction. All patients followed up for at least 3 months, and no hypertrophic scar formation was noted. Conclusion Comparing with the indirect wet dressing method, this new method is practical for covering split-thickness skin grafts, causes less pain, and provides a better experience for patients.

Due to the controversial nature of fetal bovine serum (FBS) production and safety concerns, there is a major interest in finding a potential FBS replacement, such as human platelet-rich plasma (PRP). However, traditional PRP production is largely limited by yield and is unsuitable for large-scale production. In this study, our first aim is to optimize the porcine PRP production protocol, and render it capable of manufacturing a large amount of porcine PRP that is suitable as an FBS replacement. Additionally, our secondary aim is to determine the effects of porcine PRP on human follicle dermal papilla cells (HFDPCs). In our process, the platelets are separated and concentrated via small- (with a capacity of 2.4 L/h) or large-scale preparations (with a capacity of 200–500 L/h). The porcine PRP is activated using a combination of collagen, thrombin, and calcium chloride, resulting in three distinct PRP formulations. Growth factor levels and stabilities of PRP under different treatments were measured using ELISA, MTT and real-time PCR assays. Our results showed that porcine PRP has higher growth factor levels than FBS, and is stable during freeze-drying and surfactant treatments, whereas HFDPCs treated with freshly prepared or freeze-dried PRP showed no significant difference in proliferation compared to FBS. In conclusion, our study is the first to confirm the commercial viability of porcine PRP as an FBS replacement and hair growth promoter.

Cutaneous malignant melanoma is notorious for its aggressive behavior and relatively poor outcome compared with other common skin malignancies. Acral lentiginous melanoma (ALM) accounts for at least 50% of melanoma in the Asian population and has a significantly lower survival rate. However, previous studies of the prognostic factors of melanoma-specific survival were all conducted from Western institutions. Here, we performed a retrospective analysis to investigate this issue.Fifty patients diagnosed as having clinical node-negative cutaneous malignant melanoma who underwent sentinel lymph node (SLN) biopsy at Taipei Veterans General Hospital between January 2007 and December 2018 were enrolled. Patient demographics, tumor characteristics, and lymph node characteristics were evaluated by chart review.Eighty-two percent of the melanoma in the sample population was ALM. Twelve patients (24.0%) presented at least 1 metastatic sentinel node, and the average number of retrieved SLNs was 3. Of the patients with positive SLNs who proceeded to completion lymph node dissection, only 2 (16.7%) had metastatic nonsentinel nodes (NSNs). The average follow-up time for all patients was 45 months. Recurrence and melanoma-specific death occurred in 21 patients (42.0%) and 15 patients (30.0%), respectively. Melanoma-specific survival was significantly lower in patients with ulcerative lesions (P = 0.005) and more metastatic SLNs (P = 0.036). The overall morbidity rate of completion lymph node dissection was 66.7%.The presence of ulcerations and number of metastatic SLNs were the most important prognostic factors in this ALM-dominant Asian cohort. Among patients with clinically negative nodes but positive SLNs, less than one-fourth of patients harbored metastatic NSNs. Completion lymph node dissection carries a relatively high risk of morbidity; therefore, further research regarding predictors of positive NSNs in the Asian population is necessary.

Background The aim of this study was to investigate the epidemiological and clinical characteristics of salivary gland tumors (SGTs) in a Taiwanese population and to provide data for comparison with other studies in various locations and racial populations. Methods We retrospectively analyzed the medical records of 559 patients with tumors of the salivary glands who were surgically treated from 2002 to 2017 at a single institution. Results There were 430 benign and 129 malignant tumors with a mean age of 53.5 years (range, 1-91 years). The mean age of patients with benign SGTs was 52.6 years, and the mean age of patients with malignant SGTs was 55.8 years. Most findings were similar to those reported in literature, with some variations. The salivary tumors slightly predominated in males. There were no differences in age and incidence of benign or malignant major SGTs between males and females. The frequency was 76.9% for benign tumors (430 patients) and 23.1% for malignant tumors (129 patients). The majority of the tumors occurred in the parotid gland (351 cases), followed by the submandibular gland (152 cases), the minor salivary glands (46 cases), and, lastly, the sublingual gland (10 cases). Minor SGTs occurred most frequently on the palate, with pleomorphic adenoma, the most frequent benign tumor type, and adenoid cystic carcinoma and mucoepidermoid carcinoma, the commonest malignant tumor types. Tumors of the sublingual gland were rare, but 80% were malignant. Conclusions In our series, SGTs were uncommon neoplasms that typically arose in the parotid gland. Benign tumors were far more common than malignant tumors. Pleomorphic adenoma was the most common benign tumors. Adenoid cystic carcinoma and mucoepidermoid carcinoma constituted the most common malignancies. Almost 60% of the tumors arising from minor salivary glands were malignant; thus, special care must be taken when these glands are affected.

Adipose stem cells (ASCs) show potential in the recellularization of tissue engineerined vascular grafts (TEVGs). However, whether sphingosine-1-phosphate (S1P) could further enhance the adhesion, proliferation, and antithrombosis of ASCs on decellularized vascular scaffolds is unknown. This study investigated the effect of S1P on the recellularization of TEVGs with ASCs. Human ASCs were derived from lipoaspirate. Scaffolds were derived from human umbilical arteries (HUAs) with treatment of 0.1% sodium dodecyl sulfate (SDS) for 48 h (decellularized HUAs, DHUAs). The adhesion, proliferation, and antithrombotic functions (kinetic clotting time and platelet adhesion) of ASCs on DHUAs with S1P or without S1P were evaluated. The histology and DNA examination revealed a preserved structure and the elimination of the nuclear component more than 95% in HUAs after decellularizaiton. Human ASCs (hASCs) showed CD29(+), CD73(+), CD90(+), CD105(+), CD31(&ndash, ), CD34(&ndash, ), CD44(&ndash, ), HLA-DR(&ndash, ), and CD146(&ndash, ) while S1P-treated ASCs showed marker shifting to CD31(+). In contrast to human umbilical vein endothelial cells (HUVECs), S1P didn&rsquo, t significantly increase proliferation of ASCs on DHUAs. However, the kinetic clotting test revealed prolonged blood clotting in S1P-treated ASC-recellularized DHUAs. S1P also decreased platelet adhesion on ASC-recellularized DHUAs. In addition, S1P treatment increased the syndecan-1 expression of ASCs. TEVG reconstituted with S1P and ASC-recellularized DHUAs showed an antithrombotic effect in vitro. The preliminary results showed that ASCs could adhere to DHUAs and S1P could increase the antithrombotic effect on ASC-recellularized DHUAs. The antithrombotic effect is related to ASCs exhibiting an endothelial-cell-like function and preventing of syndecan-1 shedding. A future animal study is warranted to prove this novel method.

Secondary lymphedema is associated with impaired lymph fluid drainage and remains incurable. Alternatively, cell-based therapy may pave the way for lymphedema treatment. We found 11 animal and seven human studies had been conducted from 2008 to 2018. Most studies showed great potential for this treatment modality. Emerging studies have focused on novel techniques, such as coupling cell therapy with lymph node transfer, or adding growth factors to cell therapy.

BACKGROUND Accurate assessment of breast volume is an essential component of preoperative planning in one-stage immediate breast reconstruction (IBR) for achieving breast symmetry and a satisfactory cosmetic outcome. In this study, we compared breast volume estimation using three-dimensional (3D) surface imaging with magnetic resonance imaging (MRI) to determine the accuracy of breast volume measurements. Further, a 3D printing mold for facilitating autologous breast reconstruction intraoperatively is described. METHODS Patients scheduled to therapeutic or prophylactic mastectomy with one-stage IBR, either by autologous tissue transfer or direct implant, from 2016 to 2019, were enrolled in this study. 3D surface image and MRI were performed to evaluate breast volume and shape. The results were validated by the water displacement volume of the mastectomy specimen. Finally, a 3D printing mold was designed for breast reconstruction with autologous tissue. RESULTS Nineteen women who were scheduled to have 20 mastectomies (18 unilateral and one bilateral) were included. There was a strong linear association between breast volume measured using the two different methods and water displacement of mastectomy specimens when a Pearson correlation was used (3D surface image: r = 0.925, p < 0.001; MRI: r = 0.915, p < 0.001). Bland-Altman plots demonstrated no proportional bias between the assessment methods. The coefficient of variation was 52.7% for 3D surface imaging and 59.9% for MRI. The volume of six breasts was evaluated by both measurements and the intraclass correlation coefficient was 0.689 for 3D surface image (p = 0.043) and 0.743 for MRI (p = 0.028). CONCLUSION Using 3D surface image to evaluate breast shape and volume is a quick, effective, and convenient method. The accuracy, reproducibility, and reliability of 3D surface imaging were comparable with MRI in our study. In addition, 3D-printed molds can achieve better symmetry and aesthetic outcomes in immediate autologous breast reconstructions.

BACKGROUND The study of effectiveness of adipose-derived stem cells (ASCs) in treating burn wounds is still a developing field. The process of wound contraction in areas of loose skin is a major confounding factor in the evaluation and study of burn wound healing in animal models. METHODS To evaluate the effect of local ASCs administration, deep partial thickness burn wounds were induced by 30 s application of hot copper plates in a novel skin island burn wound rat model to avoid interference from primary wound contraction. Skin islands were divided into two treatment groups-control group (n = 9) injected with PBS and ASCs-treated group (n = 9) injected with 5 × 10 ASCs intradermally. Progress in wound healing was checked at regular intervals after injury (on 1st, 2nd, 3rd, and 4th week) by measuring the mean wound area and analyzing the wound histologically and immunohistochemically, after unstitching the overlaying skin to expose the skin island. RESULTS It was found that local intradermal injection of ASCs improved burn wound healing at all given time points when compared with control groups, especially in the first 2 weeks (p < 0.05). The percentage of live follicles increased gradually in the ASCs-treated groups compared with control groups between the 3rd and 4th weeks (p < 0.05). The vascular density and proliferating cell nuclear antigen index were also significantly increased in the ASCs-treated groups. CONCLUSION Thus, in this study, a novel burn wound rat model with reduced interference from wound contraction has been put forth to investigate the therapeutic effects of local administration of ASCs on burn wound healing. Local injection of ASCs not only improved burn wound recovery but also enhanced angiogenesis and skin appendage regeneration.