Cell therapies and its derivatives as immunomodulators in vascularized composite allotransplantation.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

Turbocharging as a strategy to boost extended perforator flap vascularity in head and neck reconstruction-A report of two cases.

Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.

The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival.

BACKGROUND: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p<0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-ß1 levels (p = 0.02), and a trend toward a decrease in IL-1ß levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Evaluation of Blepharoptosis in Patients With Refractory Blepharospasm by VISA-Video Recordings, Idiosyncratic Expressions, Sensory Tricks, and Ancillary Procedures.

BACKGROUND: How to evaluate blepharoptosis concomitantly presented with refractory and uncontrollable blepharospasm? To date, there is a paucity of publications on the ideal evaluation methods. An innovative method-video recordings, idiosyncratic facial expressions, sensory tricks, and ancillary procedures (VISA)-is developed for preoperative evaluation, and the surgical outcomes are demonstrated. METHODS: A retrospective study using VISA for blepharoptosis evaluation was conducted on 51 patients with refractory blepharospasm. Based on the evaluation, patients underwent blepharoptosis correction simultaneously besides the selective myectomy and myotomy in situ of the eyelid protractors for blepharospasm. Preoperative and postoperative palpebral fissure height, margin reflex distance 1, ptosis severity, and levator function were assessed to identify the effectiveness of VISA. All the procedures were performed by the senior author C.-S.L. RESULTS: There were 42 patients diagnosed with essential blepharospasm and 9 patients with Meige syndrome. Forty-one patients (82/102 eyelids [80.4%]) had concomitant blepharoptosis and blepharospasm. Ptosis severity was mild in 21 eyelids (25.6%), moderate in 12 eyelids (14.6%), and severe in 49 eyelids (59.8%). Preoperative/postoperative (6 months) values of palpebral fissure height, margin reflex distance 1, and levator function were 4.70 ± 2.45 mm/8.35 ± 1.33 mm (P < 0.05), -0.30 ± 3.19 mm/3.73 ± 1.05 mm (P < 0.05), and 13.07 ± 2.56 mm/13.68 ± 2.34 mm (P < 0.05), respectively. Undercorrection and revision rate reported 9.8% and 3.7%, individually. CONCLUSIONS: VISA approach overcomes the difficulty of blepharoptosis assessment in patients with refractory blepharospasm. It provides useful preoperative information required for adequate blepharoptosis correction in blepharospasm surgery and yielded desirable outcomes.

Selective Myectomy and Myotomy In Situ for the Management of Refractory Blepharospasm in Meige Syndrome.

BACKGROUND: Meige syndrome is characterized by involuntary blepharospasm and varied subphenotypes of oromandibular tonic-clonic muscle contraction. Despite botulinum toxin (BTx) being the mainstay of treatment for Meige syndrome, a small subset of patients remain refractory to its effects because the disease is a form of functional blindness. An integrative surgical procedure combining selective myectomy and myotomy in situ of eyelid protractors, blepharoptosis correction, and tightening of the lower eyelid laxity was first applied to treat refractory blepharospasm in patients with Meige syndrome. MATERIALS AND METHODS: This study is a retrospective review conducted on 24 patients with refractory Meige syndrome between 2013 and 2020. Besides selective myectomy and myotomy in situ of eyelid protractors, levator plication and lateral tarsoplasty or canthopexy was performed for blepharoptosis correction and lower eyelid tightening, respectively. Patient demographics, associated diseases, medical treatment history, associated surgical procedures, final aesthetic outcomes, and therapeutic effects as reflected by changes in function disability score and Botox (BTx) treatment were thoroughly recorded and analyzed. RESULTS: The mean age of the patients was 65.2 ± 8.9 years. Twenty-one patients (87.5%) received blepharoptosis correction by levator plication with an average of 11.2 ± 2.9 mm in length. Lateral tarsoplasty was performed in 16 patients (66.7%) by pentagonal tarsal resection with an average of 3.9 ± 0.8 mm in width. Five patients (20.8%) received lateral canthopexy. Among the total of 96 operated eyelids, scar revision with fat graft was performed in 3 eyelids (3.1%). The average amount of BTx treatment decreased from 49.2 ± 12.8 U once every 2.7 ± 0.8 months before surgery to 35.4 ± 7.8 U once every 3.8 ± 0.7 months after surgery. Function disability score improved from 76.7 ± 17.5% preoperatively to 15.6 ± 9.9% postoperatively ( P < 0.001). Only 3 upper eyelids (3.1%) received scar revision and fat grafting due to minor postoperative contour depression. All patients expressed high satisfaction with both functional and aesthetic outcomes (Likert scale 4.5 ± 0.5). CONCLUSIONS: Selective myectomy and myotomy in situ of eyelid protractors combining blepharoplasty correction and lower eyelid tightening can produce long-lasting functional and aesthetic results with minimal complication in patients with refractory Meige syndrome.

Lateral Tarsoplasty for Managing Ectropion and Laxity of the Lower Eyelid.

BACKGROUND: The most challenging complication associated with lower blepharoplasty is ectropion, and the traditional lateral canthopexy or canthoplasty procedure may carry the risk of eyelid malposition or subsequent chemosis. We propose lateral tarsoplasty with a detailed description of the techniques to treat and even prevent ectropion by not involving the medial or lateral canthal ligament so as to avoid complications. MATERIALS AND METHODS: Lower eyelid laxity was analyzed with the snap-back test and distraction test before surgery. Approximately 5 mm medial to the lateral canthus, lateral tarsoplasty is performed through a full-thickness pentagonal tarsal-conjunctival resection according to the "overlapping test" for an accurate measurement of the amount of the tarsus to be resected. Seventy-two eyelids that received either ectropion correction or prevention with lateral tarsoplasty over an 8-year period at a single institution were collected and analyzed for this retrospective review. RESULTS: Lateral tarsoplasty was performed in 39 patients with a mean age of 63.8 years. Thirteen patients with 20 eyelids presented for ectropion correction, in whom 5 to 10 mm of tarsus was resected, 6.0 mm in average. The other 26 patients with 52 eyelids presented for ectropion prevention, in whom 3 to 7 mm of tarsus was resected, 4.1 mm in average. Apart from temporary mild chemosis, all patients experienced highly satisfactory results without any ectropion or malposition of the involved lower eyelids after a follow-up of 8.1 months in average. CONCLUSIONS: For patients with moderate and severe laxity of lower eyelids, lateral tarsoplasty without involvement of the lateral canthal ligament proves to be an effective way to treat and prevent lower eyelid ectropion.

The Effects of Silver-Releasing Foam Dressings on Diabetic Foot Ulcer Healing.

Diabetic foot ulcers (DFUs) are a serious complication in diabetic patients and lead to high morbidity and mortality. Numerous dressings have been developed to facilitate wound healing of DFUs. This study investigated the wound healing efficacy of silver-releasing foam dressings versus silver-containing cream in managing outpatients with DFUs. Sixty patients with Wagner Grade 1 to 2 DFUs were recruited. The treatment group received silver-releasing foam dressing (Biatain® Ag Non-Adhesive Foam dressing; Coloplast, Humlebaek, Denmark). The control group received 1% silver sulfadiazine (SSD) cream. The ulcer area in the silver foam group was significantly reduced compared with that in the SSD group after four weeks of treatment (silver foam group: 76.43 ± 7.41%, SSD group: 27.00 ± 4.95%, p < 0.001). The weekly wound healing rate in the silver foam group was superior to the SSD group during the first three weeks of treatment (p < 0.05). The silver-releasing foam dressing is more effective than SSD in promoting wound healing of DFUs. The effect is more pronounced in the initial three weeks of the treatment. Thus, silver-releasing foam could be an effective wound dressing for DFUs, mainly in the early period of wound management.

Current operative management and therapeutic algorithm of lymphedema in the lower extremities.

Lymphedema is defined as the abnormal accumulation of interstitial fluid in subcutaneous tissues resulting from cancer, cancer treatment (surgery and/or radiotherapy), infection, inflammatory disorders, obesity, and hereditary syndromes. Surgical management of lymphedema can be broadly classified into two categories, reductive surgical techniques such as direct excision, suction assisted protein lipectomy (SAPL) or radical reduction with perforator preservation (RRPP); and physiological surgical procedures such as lymphaticovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT). These techniques and their various combinations were evaluated. The results revealed patients with reversible lymphedema (ISL stage I, mild severity) benefit most from physiological procedures (LVA or VLNT) which can reduce the chance of disease progression to the chronic, solid phase. Reductive techniques such as SAPL, RPPP, or direct excision procedures should be reserved for patients with advanced - severe lymphedema (ISL stages II and especially stage III) as the surgical treatment of choice. In this study, current literature on the surgical treatment of lower extremity lymphedema is reviewed and discussed in conjunction with authors' clinical experiences. An algorithm is presented, based on clinical evidence and experience which aims to provide a structured approach to managing lower limb lymphedema.

The use of negative-pressure wound therapy over a cultured epithelial autograft for full-thickness wounds secondary to purpura fulminans in an infant.

Purpura fulminans is a serious condition that can result in severe morbidity in the pediatric population. Although autologous skin grafts remain the gold standard for the coverage of partial- to full-thickness wounds, they have several limitations in pediatric patients, including the lack of planar donor sites, the risk of hemodynamic instability, and the limited graft thickness. In Singapore, an in-house skin culture laboratory has been available since 2005 for the use of cultured epithelial autografts (CEAs), especially in burn wounds. However, due to the fragility of CEAs, negative-pressure wound therapy (NPWT) dressings have been rarely used with CEAs. With several modifications, we report a successful case of NPWT applied over a CEA in an infant who sustained 30% total body surface area full-thickness wounds over the anterior abdomen, flank, and upper thigh secondary to purpura fulminans. We also describe the advantages of using NPWT dressing over a CEA, particularly in pediatric patients.

Low-Grade Myofibroblastic Sarcoma Arising From Keloid Scar on the Chest Wall After Thoracic Surgery.

Keloids are considered as benign fibroproliferative skin tumors, and rare cases of malignancies have been reported. We present a case of low-grade myofibroblastic sarcoma arising from a recurrent painful keloid scar on the right chest wall after video-assisted thoracic surgery for pneumothorax in a 77-year-old man. Wide composite excision of the keloid, surrounding ribs, and partial diaphragm were performed. The chest wall pleural defect was reconstructed with Teflon (Chemours, Wilmington, DE), and soft tissue was reconstructed with a transverse rectus abdominis myocutaneous flap. This case highlights that refractory keloids may be considered a harbinger of malignancy.

International microsurgery simulation society (IMSS) consensus statement on the minimum standards for a basic microsurgery course, requirements for a microsurgical anastomosis global rating scale and minimum thresholds for training.

INTRODUCTION: Microsurgery is a surgical technique that uses optical magnification as well as specific instruments to address necessary reconstructive procedures in different medical specialties. The apprenticeship of this technique requires overcoming a steep learning curve. There is a need for standardization of the training criteria in microsurgery. The International Microsurgery Simulation Society (IMSS) was born in 2011, since then its main objective has been to connect the main international specialists and educators of this sub-specialty to share and discuss the ethical and scientific basis of preclinical microsurgery teaching. METHODS: In order to achieve a consensus on the minimum standards for the organization of basic microsurgery training courses, the requirements for a microsurgical anastomosis global rating scale and minimum thresholds for training, a total of nineteen independent global experts participated in a formal consultative consensus development program. The agreement criteria for each statement was established when consensus of 65-100% was reached. RESULTS: There have been established six recommendations concerning minimum standards for a basic microsurgery course, one recommendation in relation to minimum thresholds for training and four recommendations regarding the global rating scale as gold standard for a microsurgical anastomosis assessment. The eleven defined recommendations reached the agreement threshold of 65-100%. CONCLUSIONS: The development of this consensus sets the minimum recommended requirements for conducting basic microsurgery training courses, as well as suggestions for objective assessment of the learning curve and skills of trainees.

The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3ß Pathway.

Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3ß (GSK-3ß) is involved in epithelial differentiation during wound healing. This study investigated whether the enhancement of diabetic wound healing by ESWT is associated with the GSK-3ß-mediated Wnt/ß-catenin signaling pathway. A dorsal skin wounding defect model using streptozotocin-induced diabetic rodents was established. Rats were divided into 4 groups: group 1, normal controls without diabetes; group 2, diabetic controls without treatment; group 3, diabetic rats receiving ESWT; and group 4, rats receiving 6-bromoindirubin-3'oxime (BIO), a GSK-3ß inhibitor, to trigger Wnt/ß-catenin signaling. Tissue samples were collected and analyzed by immunohistochemical (IHC) staining and quantitative RT-PCR. The ESWT and BIO-treated groups both exhibited significant promotion of wound healing compared to the healing in controls without treatment. RT-PCR analysis of Wnt-1, -3a, -4, -5a, and -10 and ß-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and ß-catenin levels were significantly increased in the ESWT and BIO treatment groups compared to the control groups. ESWT enhancement of diabetic wound healing is associated with modulation of the GSK-3ß-mediated Wnt/ß-catenin signaling pathway.

Elbow Reconstruction With Compression Plate Arthrodesis and Circumferential Muscle-Sparing Latissimus Dorsi Flap After Tumor Resection: A Case Report.

BACKGROUND: The goals of limb-sparing surgery in the setting of extremity malignancies are 2-fold: oncological clearance and the rehabilitation of function and aesthetics. Treatment success should be defined by the extent of restoration of the patient's premorbid function for reintegration into society. METHODS: We would like to report an unusual case of a patient with a chronically ankylosed elbow with joint invasion by basal cell carcinoma which resulted from malignant transformation of an overlying, long-standing wound due to inadequately treated septic arthritis from his childhood years. RESULTS: Following R0 resection, upper limb shortening and compression plate elbow arthrodesis were performed with the aim of restoring the degree of upper limb function that the patient had been accustomed to preoperatively. The resultant circumferential defect was then closed with a contralateral, free muscle-sparing latissimus dorsi flap. CONCLUSIONS: Functional preservation may therefore be more important than the mere restoration of anatomical defects in these especially challenging situations.

Stepwise training for reconstructive microsurgery: the journey to becoming a confident microsurgeon in singapore.

Microsurgery training in Singapore began in 1980 with the opening of the Experimental Surgical Unit. Since then, the unit has continued to grow and have held microsurgical training courses biannually. The road to becoming a full-fledged reconstructive surgeon requires the mastering of both microvascular as well as flap raising techniques and requires time, patience and good training facilities. In Singapore, over the past 2 decades, we have had the opportunity to develop good training facilities and to refine our surgical education programmes in reconstructive microsurgery. In this article, we share our experience with training in reconstructive microsurgery.

Development of a five-day basic microsurgery simulation training course: a cost analysis.

The widespread use of microsurgery in numerous surgical fields has increased the need for basic microsurgical training outside of the operating room. The traditional start of microsurgical training has been in undertaking a 5-day basic microsurgery course. In an era characterised by financial constraints in academic and healthcare institutions as well as increasing emphasis on patient safety, there has been a shift in microsurgery training to simulation environments. This paper reviews the stepwise framework of microsurgical skill acquisition providing a cost analysis of basic microsurgery courses in order to aid planning and dissemination of microsurgical training worldwide.

The chicken aorta as a simulation-training model for microvascular surgery training.

As a technically demanding skill, microsurgery is taught in the lab, in the form of a course of variable length (depending on the centre). Microsurgical training courses usually use a mixture of non-living and live animal simulation models. In the literature, a plethora of microsurgical training models have been described, ranging from low to high fidelity models. Given the high costs associated with live animal models, cheaper alternatives are coming into vogue. In this paper we describe the use of the chicken aorta as a simple and cost effective low fidelity microsurgical simulation model for training.

Assessment of microsurgery competency-where are we now?

In the last decade surgical training is being revolutionized by two novel concepts that have been introduced to almost all branches of surgery including and most recently to microsurgery. These two concepts are: objective assessments of surgical skills and the nurturing of surgical skills in a simulation laboratory setting. Acquiring surgical skills in the laboratory setting can help move the microsurgical learning curve from the patient to the laboratory and this will in turn improve patient safety. In order to optimize microsurgical training through a competency based training programme, it is imperative for microsurgical educators to understand microsurgical skill acquisition. This requires accurate objective assessment tools that can define and quantify microsurgical competency. This article aims to review the current literature on the various objective assessment tools adapted for microsurgery and attempt to identify the gaps that need to be addressed by research in microsurgical education to establish the ideal objective assessment tool.