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To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on angiogenesis and lymphangiogenesis in oral carcinoma. Immunohistochemistry was used to study the expression of CEACAM1, LYVE1 and CD31, double-labelling immunofluorescence was used to detect the co-expression of CEACAM1 and LYVE1, and double-labelling immunohistochemistry was performed to observe the co-expression of LYVE1 and CD31 in vessels. Membranous CEACAM1 was expressed in well-differentiated squamous cell carcinoma and cytoplastic CEACAM1 in poorly and moderately differentiated carcinoma (P<0.05). More CEACAM1-positive vessels were observed in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). Co-expression of CEACAM1 and LYVE1, LYVE1 and CD31 in vessels was more common in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). CEACAM1 has different distribution in oral carcinoma. Membranous CEACAM1 inhibits angiogenesis and lymphangiogenesis, but cytoplasmic CEACAM1 promotes angiogenesis, and even promotes lymphangiogenesis by mediating the transformation of vascular endothelial cells (VECs) into lymphatic endothelial cells (LECs). [ABSTRACT FROM AUTHOR]

A perforator is a vessel that travels through muscle and perfuses the skin. Perforator flaps require intramuscular dissection and can be used as pedicled or free flap. With improved understanding of microvasculature, they can be tailored to have multiple skin paddles, multiple components, or shaped to conform to any defect. Reliable perforator flap-based reconstruction is a meticulous microvascular technique, ultimately allowing the surgeon to harvest any flap in a freestyle fashion and transplant to any recipient vessel. New technologies improve the safety and reproducibility of this type of reconstruction., Competing Interests: Disclosure The authors have no relevant or material financial that relates to the research described in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Osteoradionecrosis (ORN) is an aggressive sequela of head and neck cancer, treatment of which focuses on functional restoration and quality-of-life (QoL). This study aims to identify risks for poor QoL in ORN reconstruction and build a chronologic, longitudinal framework for QoL., Methods: A prospective database of reconstructions performed by the senior author was reviewed from 2015-2023. QoL metrics (University of Washington [UWQoL]v4) were prospectively administered prior to surgery, one year post-operatively, and each yearly follow-up., Results: 56 ORN patients were included (average 58.2years, mean 6,412Gy radiation). Reconstruction commonly was achieved with the fibula(55.4%) and anterolateral-thigh flaps(37.5%). The total complication rate was 23.2%, median 10.7mo post-operatively.Both "health-related QoL in comparison with prior to cancer diagnosis" (62.5 vs 43.5;p=0.030) and "Overall QoL during the past 7-days" (50.5 vs 41.7;p=0.029) were higher post-ORN reconstruction than before. Physical-QoL was higher pre-cancer reconstruction (79.0) than prior to ORN reconstruction (50.6;p<0.001) and following reconstruction (52.5;p=0.001). Social-emotional function was higher following ORN reconstruction compared to pre-reconstruction (68.7 vs 59.6;p=0.010).On multi-variate analysis, both post-operative social-emotional and physical function were impacted by betelnut use (p=0.038;p=0.025). Poor improvement in QoL from pre to post-ORN reconstruction were affected by maxilla involvement (p=0.048), fistula (p=0.004), and hardware issues (p=0.001)., Conclusions: Our longitudinal experience trended decline in QoL at ORN diagnosis with gradual improvement following reconstruction, with eventual social-emotional, pain, anxiety, chewing, and global-QoL significantly improved following surgery. Betelnut was a risk factor for poor post-operative QoL. Maxillary involvement, post-op fistula and hardware issues were risks for non-improvement in QoL., Competing Interests: Financial disclosures, conflict of interest, products: The authors have no disclosures, conflict of interest, or products, to declare., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background:  Over the past two decades, with the introduction of the perforator flap concept and advances in flap dissections, lower extremities have emerged as the preferred soft tissue flap donor sites. As a modern and high-volume microsurgical center, and the senior author being one of the pioneers and advocates for the use of lower extremity flap donor sites, we aim to investigate the role of latissimus dorsi (LD) free flap in head and neck reconstruction within our current practice., Methods:  All free LD flaps used for head and neck reconstruction performed by a single surgeon between January 2010 and June 2023 were reviewed for their indications and immediate and short-term outcomes., Results:  A total of 1,586 head and neck free flap reconstructions were performed, and 33 free LD flaps were identified. The patients' median age was 53 (interquartile range [IQR] 48.5-63.5) years. Twenty-nine (87.9%) flaps were used to reconstruct oro-maxillo-facial and four (12.1%) flaps were used to reconstruct scalp defects. Most patients had prior radiation ( n  = 28, 84.8%), neck dissection ( n  = 24, 72.7%), and multiple previous head and neck flap reconstructions with a median of 3.0 (IQR 3.0-3.5) previous flaps. Six (18.2%) LD flaps were used to replace failed flaps from other donor sites. No major complications such as total flap failure or takebacks, and no need for vein grafts but three (9.1%) had flap marginal necrosis. Other complications included one flap dehiscence (3.0%), one orocutaneous fistula (3.0%), two wound infections (6.1%), three plate exposures (9.1%), and three patients who developed local recurrence (9.1%). The median patient follow-up time was 16 (IQR 5-27) months., Conclusion:  This retrospective study demonstrates the role of LD free flap in head and neck reconstruction as a reliable and versatile backup soft tissue flap when workhorse flaps from lower extremity donor sites are either unavailable or unsuitable., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To examine the effectiveness of health education and counseling on the stages of change, decisional balance, and smoking cessations elf-efficacy in smokers with no intention of quitting., Methods: A prospective self-controlled design was conducted between December 2020 and December 2022. The research period was divided into a control stage (first to fourth weeks) and an experimental stage (fifth to eighth weeks). Patients with coronary artery disease (CAD) and habitually smoked were recruited. Pearson correlation and a one-factor repeated-measurement analysis were performed to assess the effectiveness of the intervention., Results: In total, 108 male CAD patients with a mean age of 58.1 years were recruited. After 4 weeks of the intervention, 55 (51%) exhibited behavior change (X 2 = 18.03, p = .001). The decisional balance and smoking cessation self-efficacy scores significantly improved in the experimental stage. No significant differences were observed in the control stage., Conclusions: Four weeks of health education and counseling could effectively improve participants' stage of change, decisional balance, and smoking cessation self-efficacy., Practice Implication: Healthcare professionals can play key roles in helping CAD patients successfully quit smoking through individual education and counseling., Competing Interests: Declaration of Competing Interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to evaluate quality of life (QOL) in patients with locally advanced oral cancer who underwent surgical resection followed by simultaneous double free flap reconstruction., Methods: Institutional database was reviewed from 2015 to 2021 and prospectively collected University of Washington Quality of Life data that were extracted for patients who met the inclusion criteria. Mean, composite, and best percentage scores were computed. Wilcoxon signed rank test was used to analyze differences between groups., Results: Thirteen patients completed the assessment, all of them being male with a mean follow-up of 2.2 ± 1.2 years. Most common double free flap combination was fibula osteoseptocutaneous flap and anterolateral thigh flap (n = 11). Improvement in pain ( P = 0.01) domain score with decline in speech ( P = 0.01) and taste ( P = 0.02) was noted along with an overall decline in QOL ( P = 0.001) after cancer diagnosis. A decrease in physical function was seen postoperatively. Chewing and saliva were the most cited postoperative patient-reported domain affecting QOL., Conclusions: In double free flap reconstructed patients, in the postoperative phase, pain scores improved, whereas speech and taste scores declined. The overall health-related QOL declined compared with before cancer diagnosis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Successive osteoseptocutaneous fibula transfers for jaws reconstruction are rare but important options. This study contributes patient-reported and clinical outcomes, as well as systematically reviews all existing reports., Methods: All sequential fibula transfers performed by the senior author were reviewed from a prospectively managed database, including University of Washington quality of life (UWQoL). Systematic review was conducted in PubMed and Cochrane databases for similar publications., Results: Eighteen patients (average age 51.5 years) received sequential fibulas (mean 4.7 years between reconstructions). Secondary fibulas more often had benign indications (72.2% vs. 33.3%, p = .04), most commonly osteoradionecrosis (38.9%). At a mean follow-up of 30.5 months, the average interincisal distance increased from 21.8 to 27.6 mm, and 92.3% tolerated an oral diet following the second fibula. Eight patients completed the UW-QoL before and after the second fibula, and three prior to the first fibula. Composite physical function was significantly decreased from 96.7 prefibula reconstruction to 63.3 following the first (p < .001) and 64.2 after the second fibula (p < .001). There were no differences in other domains. The systematic review yielded six articles reporting 56 patients (mean 39 months between fibulas). Secondary fibulas were performed for repeat malignancy (45%) and osteoreadionecrosis (39%), resulting in elevated tube feeding from 20% following the first to 39% following the second, but overall high quality of life in two studies., Conclusions: Sequential osteoseptocutaneous fibula reconstructions of jaws are often performed for benign indications such as osteoradionecrosis. Overall function and QoL are comparable with those following the first fibula transfer., (© 2024 Wiley Periodicals LLC.)

Soft tissue reconstruction of the upper extremity requires consideration of wound bed status, varied anatomic composition, future function and tissue match, whether in thickness, pliability or involvement of other tissue components. Of the options available, microvascular free tissue flaps allow maximal customizability with the avoidance of long-term donor site morbidity. Free tissue transfers have evolved, given increased surgical proficiency, from direct vessel-based flaps to septocutaneous vessel-based flaps, to musculocutaneous perforator flaps, and most recently to free-style free flaps. With increases in technical complexity come limitless alternatives. We documented the progression of free flap upper extremity reconstruction in recreating form and function of the upper extremity. The foundations laid should allow surgeons the freedom and versatility to choose the most faithful restoration of the defect and produce the best functional and aesthetic results., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Conflict of Interest J.J.H. and J.-P.H. are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Background: Microsurgical great toe-to-thumb transfer (mGTT) is a widely used procedure when immediate replantation of thumb is not feasible. The aim of this study was to investigate the alteration of plantar pressure profile of the donor foot after mGTT., Methods: Twenty patients receiving microsurgical great toe-to-hand transfer between 1985 to 2014, and 16 healthy subjects were recruited. Group 1 consisted of 20 feet receiving mGTT, whereas group 2 consisted of 32 normal feet as control. The flap design in this study was to preserve 1 cm of the proximal phalanx to maintain the attachment of the plantar aponeurosis and intrinsic muscles. The Taiwan Chinese version of the Foot Function Index was used for patient-reported outcome measurement. A novel Emed-X system was used for dynamic plantar pressure measurement. A total of four parameters were collected, including peak pressure, contact area, contact time, and pressure-time integral., Results: In group 1, the peak pressure redistributed under the first metatarsal bone and was significantly higher than group 2 ( P < 0.05). There was no significant change of the contact area between the midfoot region of group 1 and group 2 ( P > 0.05). Furthermore, similar foot clearance efficiency was demonstrated in group 1 and group 2 ( P > 0.05)., Conclusions: The windlass effect of the foot will not be affected when performing mGTT with preservation of 1 cm of the proximal phalanx. Therefore, this surgical procedure is highly recommended for clinical application., Competing Interests: This study was supported by Minister of Science and Technology, Taiwan, R.O.C. (Grant number: 110WHK0510154), Chang Gung Medical Foundation (Grant number: CMRPG3G1422), and Lo Hsu Medical Foundation. The other authors have no financial interest to declare., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Fibula Jaw-in-a-Day (JIAD) is considered the most advanced approach for segmental mandibular defect reconstruction and dental rehabilitation. However, it has limitations and challenges for further pursuit. We propose Fibula Jaw-during-Admission (JDA) as a solution., Materials and Methods: From 2019 to 2021, six patients received fibula "Jaw-during-Admission." Segmental mandibulectomy, fibula transfer, and immediate dental implantation were performed simultaneously during a single surgery. Intraoral scans were used to fabricate temporary light occlusion contact dental prostheses while on the ward prior to discharge during the first and second week post operation. The prostheses were installed before discharge and changed to permanent ones with normal occlusal contact in the clinic at about six months after X-ray confirmation of bone healing., Results: All six surgeries succeeded. Four patients received palatal muco-periosteal graft after debridement of peri-implant overgrown granulation tissue. Follow-up ranged from 12 to 34 months (average 21.2 months) and revealed good function and appearance in all patients., Conclusion: Fibula JDA is superior to the Fibula JIAD approach for simultaneous mandibular reconstruction with fibula and dental rehabilitation. There is no need for postoperative intermaxillary fixation. The surgery can be performed more reliably with less stress. It provides an additional opportunity for dental rehabilitation if initial dental prosthesis installation during JIAD fails. Postreconstruction intraoral scans provide greater precision and more flexibility in milling dental prosthesis which are mapped to the reconstructed mandible during the postoperative period., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Although vascularized composite allotransplantation (VCA) has been the focus of many animal studies, further research is needed to determine the potential for a generalized model and immunosuppression regimen that applies across different donor-recipient combinations. In this study, the authors evaluated the outcome of VCAs performed on reciprocal rodent donor-recipient combinations., Methods: VCA was performed in rats using Lewis and Brown Norway (BN) donor-recipient pairs, under the previously reported antilymphocyte serum/cyclosporine/adipose-derived stem cell regimen. Similarly, a published co-stimulatory blockade/rapamycin regimen was performed on the mouse VCA model between Balb/C and C57BL/6 strains., Results: To accommodate the active behaviors of BN recipients, the allograft had to be modified and inset to the neck instead of to the groin. The tolerogenic regimen did not provide the same benefits for BN rats as it did for Lewis recipients. Increasing antilymphocyte serum dose and extending the duration of cyclosporine administration from 10 to 21 days significantly prolonged allograft survival and induced donor-specific tolerance. In mice, the co-stimulatory blockade/rapamycin regimen produced inferior VCA outcomes in BALB/c recipients than in C57BL/6 recipients. In both rats and mice, the authors identified an association between the tolerance outcome and the peripheral chimerism measured on postoperative day 30., Conclusions: Reciprocal donor-recipient combinations led to different responses toward the immunosuppression regimen and varied VCA outcomes. Sustained donor chimerism that remained in circulation for 1 month after surgery supported long-term VCA survival. Modification of the model and immunosuppression regimen accordingly is recommended., Clinical Relevance Statement: Various donor-recipient combinations respond differently to the immunosuppression regimens. Maintaining donor chimerism for 30 days after surgery improves VCA survival. It is recommended to tailor the immunosuppression regimen based on the recipient's background to optimize outcomes., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Free flap monitoring is essential for postmicrosurgical management and outcomes but traditionally relies on human observers; the process is subjective and qualitative and imposes a heavy burden on staffing. To scientifically monitor and quantify the condition of free flaps in a clinical scenario, we developed and validated a successful clinical transitional deep learning (DL) model integrated application., Material and Methods: Patients from a single microsurgical intensive care unit between 1 April 2021 and 31 March 2022, were retrospectively analyzed for DL model development, validation, clinical transition, and quantification of free flap monitoring. An iOS application that predicted the probability of flap congestion based on computer vision was developed. The application calculated probability distribution that indicates the flap congestion risks. Accuracy, discrimination, and calibration tests were assessed for model performance evaluations., Results: From a total of 1761 photographs of 642 patients, 122 patients were included during the clinical application period. Development (photographs =328), external validation (photographs =512), and clinical application (photographs =921) cohorts were assigned to corresponding time periods. The performance measurements of the DL model indicate a 92.2% training and a 92.3% validation accuracy. The discrimination (area under the receiver operating characteristic curve) was 0.99 (95% CI: 0.98-1.0) during internal validation and 0.98 (95% CI: 0.97-0.99) under external validation. Among clinical application periods, the application demonstrates 95.3% accuracy, 95.2% sensitivity, and 95.3% specificity. The probabilities of flap congestion were significantly higher in the congested group than in the normal group (78.3 (17.1)% versus 13.2 (18.1)%; 0.8%; 95% CI, P <0.001)., Conclusion: The DL integrated smartphone application can accurately reflect and quantify flap condition; it is a convenient, accurate, and economical device that can improve patient safety and management and assist in monitoring flap physiology., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GB declared a past co-authorship with the authors H-YC, MRA, C-HL and F-CW., (Copyright © 2023 Cheng, Anggelia, Lin and Wei.)

Vascularized composite allotransplantation has great potential in face transplantation by supporting functional restoration following tissue grafting. However, the need for lifelong administration of immunosuppressive drugs still limits its wide use. Modified mRNA (modRNA) technology provides an efficient and safe method to directly produce protein in vivo . Nevertheless, the use of IL-10 modRNA-based protein replacement, which exhibits anti-inflammatory properties, has not been shown to prolong composite facial allograft survival. In this study, IL-10 modRNA was demonstrated to produce functional IL-10 protein in vitro , which inhibited pro-inflammatory cytokines and in vivo formation of an anti-inflammatory environments. We found that without any immunosuppression, C57BL/6J mice with fully major histocompatibility complex (MHC)-mismatched facial allografts and local injection of IL-10 modRNA had a significantly prolonged survival rate. Decreased lymphocyte infiltration and pro-inflammatory T helper 1 subsets and increased anti-inflammatory regulatory T cells (Tregs) were seen in IL-10 modRNA-treated mice. Moreover, IL-10 modRNA induced multilineage chimerism, especially the development of donor Treg chimerism, which protected allografts from destruction because of recipient alloimmunity. These results support the use of monotherapy based on immunomodulatory IL-10 cytokines encoded by modRNA, which inhibit acute rejection and prolong allograft survival through the induction of donor Treg chimerism., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel-drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects.

Objective: The Advance Care Planning Engagement Survey (ACP-ES) has proven effective in evaluating individuals' engagement in advance care planning (ACP). However, a Traditional Chinese version of ACP-ES (ACPES-TC) has not yet been developed. Therefore, this study aimed to translate and preliminarily validate the ACPES-TC in the Taiwanese context. Material and Methods: A forward and backward translation process was conducted. The translated questionnaire was confirmed by clinical and academic experts. The ACPES-TC was then evaluated for its reliability and validity with participants in the community and from an outpatient clinic in a medical center in Northern Taiwan. The participants comprised healthy people aged 20 to 30 years and patients ≥55 years old, recruited from September 17 to October 28, 2019. Results: Seventy people were recruited, including 20 people aged 20 to 30 years in the community and 50 patients ≥ 55 years old from clinics. The ACPES-TC scores are significantly higher among those of older age, having financial independence, and under long-term medication ( p  < .05). The patients' preference for health-related decision-making is significantly correlated with the ACPES-TC score; the point-biserial correlation coefficient is 0.46 ( p  < .001). The discriminant and criterion-related validities are verified. The ACPES-TC demonstrated a good internal consistency (Cronbach's α .97), acceptable one-week test-retest reliability (overall intraclass correlation coefficient 0.86), and low practice effect between the test and retest (Cohen's d .43). Conclusion: The overall reliability and validity of the ACPES-TC are fair, which could be used to evaluate the patients' engagement in ACP in Taiwan. However, further studies with a full-scale psychometric evaluation are needed.

Asian upper blepharoplasty is one of the most commonly requested procedures in Asian patients. Many incisional and suture methods have been described in the literature. While the suture method is advantageous for its simplicity and quick recovery, the incision method is more versatile and able to deliver predictable and reproducible results for Asian patients presenting with a diverse range of anatomy and requests. Accordingly, the incision method remains the preferred approach for many surgeons performing Asian upper blepharoplasty. In this paper, we detail our open incision hinge upper blepharoplasty technique to create dynamic upper eyelid creases in Asian patients. The surgical videos associated with this paper present our surgical technique in detail, highlighting technical refinements and surgical nuances to perform the surgery precisely and predictably. The conceptual core of our approach is the use of a vascularized orbital septum as a flap to create a fibrous extension from the levator aponeurosis to the dermis at the location of eyelid crease. This vascularized flap securely connects the posterior lamella with the anterior lamella to securely form the eyelid crease with eye opening. This most accurately recreates the anatomy that is present in attractive Asian patients with naturally occurring double eyelid and predictably creates a dynamic and crisp upper eyelid crease. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Objectives: Mandibular defects involving the central segment are challenging. This study analyzes the impact of defect extent and reconstruction method on quality of life (QOL) and obstructive sleep apnea (OSA)., Materials and Methods: Twenty-nine ameloblastoma patients received segmental mandibulectomy involving the C-segment and immediate fibula free flap reconstruction were recruited. Defects: (C: 2, LC: 11, LCL: 19). Mean defect length: 8.79 cm (± 2.34). Inset: Low-single-barrel (n: 19), with secondary distraction osteogenesis (n: 8/19), high-single-barrel (n: 7), double barrel (n: 3). Patients were surveyed using University of Washington Quality of Life (UW-QOL) and Berlin risk of postoperative sleep apnea questionnaires., Results: Flap failure: None. Mean follow-up: 109.6 ± 92.8 months., Uw-Qol: Physical function 91.83 (± 14.92); social function 90.17 (± 17.19). No statistical difference between C, LC, and LCL was found, but C group which received low-single-barrel had the lowest score in appearance and chewing domains. In health-related QOL (HR-QOL) compared with 1 month before cancer, 69% reported best results. "Appearance" was the most important issue for the past 7 days, followed by "Chewing," prevailing in LC and C groups that predominately reconstructed by low-single-barrel. Berlin score: 7 patients (4 LCL, 3 LC≥8 cm) were at high risk for postoperative OSA., Conclusion: "Like-with-like" reconstruction with immediate endosteal dental implants yields the best results. Inset of fibula bone could affect outcomes, favoring double-barrel or single-high-barrel inset. Appearance and chewing remain the main concerns, largely, in those with low-single-barrel inset and no dental restoration. After long/extensive LCL and LC mandibulectomies, postoperative OSA warrants further investigation, and modification of resection/reconstruction techniques., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

Background: The role of regulatory T cells (Treg) in tolerance induction of vascularized composite allotransplantation (VCA) remains unclear. This study was designed to examine characteristics of Treg after VCA and their capacity to rescue allografts from rejection., Methods: Osteomyocutaneous allografts were transplanted from Balb/c to C57BL/6 mice. All mice received costimulatory blockade and a short course of rapamycin. To elucidate the role of Treg for tolerance induction, Treg depletion was performed at postoperative day (POD) 0, 30, or 90. To assess capacity of Treg to rescue allografts from rejection, an injection of 2 × 106 Treg isolated from tolerant mice was applied., Results: Eighty percent of VCA recipient mice using costimulatory blockade and rapamycin regimen developed tolerance. The tolerant recipients had a higher ratio of circulating Treg to effector T cells and elevated interleukin-10 at POD 30. A significantly higher rejection rate was observed when Treg were depleted at POD 30. But Treg depletion at POD 90 had no effect on tolerance. Treg from tolerant recipients showed stronger suppressive potential and the ability to rescue allografts from rejection. Furthermore, transplanted Treg-containing skin grafts from tolerant mice delayed rejection elicited by adoptively transferred effector T cells to Rag2-/- mice., Conclusions: Circulating Treg are crucial for inducing VCA tolerance in the early posttransplant phase, and allograft-residing Treg may maintain tolerance. Treg may, therefore, serve as a potential cellular therapeutic to improve VCA outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The anterolateral thigh (ALT) flap is a popular flap for lower extremity reconstruction despite its varied pedicle anatomy. Beyond its use for soft tissue coverage, using the chimeric flap concept, the ALT flap is useful for tendon and ligament reconstruction and the creation of a gliding surface with the fascia lata component. The vastus lateralis muscle can be included for dead-space obliteration. The main pedicle is long and is a similar size match for major artery reconstruction. If several perforators are available, a split flap could be fashioned into a multitude of shapes all arising from the same pedicle., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Summary: The vascularized fibular flap has been the mainstay for mandibular reconstruction for over 30 years. Its latest evolutionary step is the jaw-in-a-day operation, during which the fibula flap and dental prosthesis restoration are performed in a single stage. Computer-aided design and manufacturing technology in mandibular reconstruction has gained popularity, as it simplifies the procedure and produces excellent outcomes. However, it is costly, time-consuming, and limited in cases that involve complex defects, including bone and soft-tissue coverage. Moreover, it does not allow for intraoperative changes in the surgical plan, including defect size and recipient vessel selection.The authors describe their approach, including a conventional technique for fibula osteoseptocutaneous flap harvest without the need for a premanufactured cutting guide, using bundled wooden tongue spatulas instead, a stereolithographic model to customize commercially ready-made reconstruction plates, and two pieces of resin to maintain occlusive alignment of the remaining jaw segments during mandibular osteotomy. Dental implants are inserted free-hand. Vector guides are then connected to the implants following insertion into the fibula to confirm acceptable alignment and subsequently replaced with scan sensors. An intraoperative digital scan is used to design and to produce a dental prosthesis by in-house milling of a polymethylmethacrylate block. From our 10-case experience over the past 3 years, we have found that our approach offers a reliable method that matches the excellent outcomes seen using full computer-assisted design and manufacturing technology. It is time- and cost-effective, not limited to relatively simple jaw defects, and can readily accommodate intraoperative changes of surgical plan., Competing Interests: Disclosure:The authors have no conflict of interest to declare., (Copyright © 2021 by the American Society of Plastic Surgeons.)

The role of the vascularized bone marrow component as a continuous source of donor-derived hematopoietic stem cells that facilitate tolerance induction of vascularized composite allografts is not completely understood. In this study, vascularized composite tissue allograft transplantation outcomes between recipients receiving either conventional bone marrow transplantation (CBMT) or vascularized bone marrow (VBM) transplantation from Balb/c (H2d) to C57BL/6 (H2b) mice were compared. Either high- or low-dose CBMT (1.5 × 10 8 or 3 × 10 7 bone marrow cells, respectively) was applied. In addition, recipients were treated with costimulation blockade (1 mg anti-CD154 and 0.5 mg CTLA4Ig on postoperative days 0 and 2, respectively) and short-term rapamycin (3 mg/kg/day for the first posttransplant week and then every other day for another 3 weeks). Similar to high-dose conventional bone marrow transplantation, 5/6 animals in the vascularized bone marrow group demonstrated long-term allograft survival (>120 days). In contrast, significantly shorter median survival was noted in the low-dose CBMT group (~64 days). Consistently high chimerism levels were observed in the VBM transplantation group. Notably, low levels of circulating CD4 + and CD8 + T cells and a higher ratio of Treg to Teff cells were maintained in VBM transplantation and high-dose CBMT recipients (>30 days) but not in low-dose VBM transplant recipients. Donor-specific hyporesponsiveness was shown in tolerant recipients in vitro. Removal of the vascularized bone marrow component after secondary donor-specific skin transplantation did not affect either primary allograft or secondary skin graft survival.

An unprecedented number of health care providers have been infected and many have died during the COVID-19 pandemic. Reconstructive microsurgeons from different surgical backgrounds often are involved in the care of known COVID-19 and high-risk patients. The need for a magnification loupe/microscope makes it difficult for them to wear recommended personal protection equipment, increasing the risk of exposure. Although advanced technologies are available, they have not been exploited effectively. To date, no safety guidelines are available for safe reconstructive microsurgical procedures in high-risk operations/known COVID-19 patients-particularly, to address operations risk and COVID-19 status of the patients, who would operate, how many should be involved, how to equip the surgeons for the procedure, when to operate as the procedure unfolds, how to adapt surgical techniques to reduce exposure risk, and can advanced technology be used to minimize exposure. A set of safety recommendations were thus developed based on literature review and firsthand knowledge of safety procedures during the COVID-19 pandemic. Current understanding of COVID-19 virology can optimize surgical team buildup and dynamics. Operating smaller teams (in a sequential style), minimizing the use of aerosols-generating devices, and modifying surgical plan and flap selection could aid in diminishing the risk of exposure and in conserving resources. Modifications in loupes design, and the combined wear of surgical mask and N95 respirators, and efficient use of "buddy system" could aid in protecting surgeons during donning and doffing. "Remote operating" is a novel concept of using a surgical robot to maximize surgeons' safety during COVID-19 pandemic., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objectives: Peripheral arterial disease (PAD) is characterised by arterial occlusion and fibrosis in the lower extremities. Extracellular volume matrix fraction (ECV) is a biomarker of skeletal muscle fibrosis, but has not been applied to the lower extremities with PAD. This study investigated the clinical feasibility of using ECV for calf muscle fibrosis quantification by comparing normal controls (NC) and PAD patients., Methods: From October 2016 to December 2017, we recruited patients with PAD, and patients with head and neck cancer receiving fibular flap as NC group. All participants underwent magnetic resonance imaging (MRI) to determine the ECV of the calves and the differences between the NC and PAD groups. ECV was calculated from T1 values at steady-state equilibrium, defined as the point in time after contrast agent injection when the variance of T1 relaxation time in blood and muscle becomes less than 5%., Results: A total of 46 patients (18 in the NC group and 28 in the PAD group) were recruited. Steady-state equilibrium was reached at 11-12 min after contrast agent injection. The NC group had significantly lower mean ECV than the PAD group (12.71% vs. 31.92%, respectively, p < 0.001). In the PAD group, the mean ECV was slightly lower in patients with collateral vessels than in those without (26.58% vs. 34.88%, respectively, p = 0.047)., Conclusion: Evaluation of skeletal fibrosis in PAD using ECV is feasible. ECV can help identify PAD patients with collateral vessel formation and lay the foundation for future research in PAD management., Key Points: • Steady-state equilibrium for ECV measurement of the lower limbs can be reached at around 11-12 min. • Quantification of lower limb muscle fibrosis by measuring ECV is clinically feasible and can be used to differentiate between patients with PAD and histologically proven normal controls. • ECV can differentiate PAD patients with or without visible collateral vessels, further expanding its role in identifying the presence of collateral supply in clinical decision-making.

Chimerism has been associated with the induction and maintenance of tolerance to vascularized composite allotransplants (VCA). Although most VCA studies have examined chimerism using flow cytometry, we proposed that precision in the measurement of chimerism may be better approximated when complimentary polymerase chain reaction (PCR) is applied to a specific short tandem repeat (STR). We identified a STR, D10Rat25, which exhibited a ~20 bp difference in length between two rat strains (BN and LEW) often utilized as the donor and recipient in many allotransplantation studies. D10Rat25 was PCR-amplified and quantified with capillary electrophoresis. With pure LEW and BN DNA, a standard curve was constructed to measure chimerism with good linearity. When applied to rat VCA, the relationship between systematic (in peripheral blood) or local (at specific organ/tissues) chimerism to allograft outcomes was noted. We found that peripheral chimerism was elevated by up to ~9% postoperative month 1 (POM 1) but then reduced regardless of the final VCA outcome. However, differences in VCA skin chimerism between early rejection and POM 1 (shown as Δ Chimerism POM1-ER ) were notable with respect to VCA outcomes. ROC analysis identified the optimum cutoff value as 17.7%. In summary, we have developed a reliable method to quantify the percentage of BN cells/DNA in BN-LEW chimeras. The detection limit was characterized, and the acquired data were comparable with flow cytometry. This method can be applied to solid organ and composite tissue allotransplantation studies., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Hui-Yun Cheng et al.)

Peripheral nerve regeneration following injury is often slow and impaired, which results in weakened and denervated muscle with subsequent atrophy. Human Wharton's jelly mesenchymal stem cells (hWJ-MSC) have potential regenerative properties which, however, remain unknown in mouse nerve recovery. This study investigated the effect of the topical application of hWJ-MSC onto repairing transected sciatic nerves in a mouse model. Human adipocyte-derived stem cells (hADSC) were used as a positive control. The sciatic nerve of BALB/c mice was transected at a fixed point and repaired under the microscope using 10-0 sutures. hWJ-MSC and hADSC were applied to the site of repair and mice were followed up for 1 year. The hWJ-MSC group had significantly better functional recovery of five-toe spread and gait angles compared with the negative control and hADSC groups. hWJ-MSC improved sciatic nerve regeneration in a dose-dependent fashion. The hWJ-MSC group had a better quality of regenerated nerve with an increased number of myelinated axons throughout. hWJ-MSC appear to be safe in mice after 1 year of follow-up. hWJ-MSC also expressed higher levels of neurotrophic factor-3, brain-derived neurotrophic factor, and glial-derived neurotrophic factor than hADSC. hWJ-MSC may promote better nerve recovery than hADSC because of this upregulation of neurotrophic factors.

Objective: Kinesin superfamily member 4 (Kif4), a conventional kinesin, is a microtubule-dependent molecular motor. The active movement of Kif4 participates in several cellular functions, including DNA repair, mitosis, the transport of macromolecules, survival of neurons and even tumorigenesis and progression. However, the role of Kif4 in monocyte/macrophage cells has not been reported. Our work aimed to increase understanding and further investigations of Kif4 in monocyte/macrophage cells., Materials and Methods: RAW264.7 cells were transfected with Kif4 small interfering RNA (siRNA), and whole genome expression microarray analysis was employed to analyze gene expression after cells treatment with or without Kif4 siRNA., Results: Our data found multiple differentially expressed genes which were enriched in the top 5 biological processes about innate immune response, immune response, response to interferon-beta, immune system process and cellular response to interferon-beta. 23 most significant pathways had been identified and enriched pathways indicated enrichment in peroxisome, lysosome, fatty acid metabolism, cell adhesion molecules and so on., Conclusions: Our work may help understand the roles of Kif4 in monocyte/macrophage cells and would give useful information on basic research and the function of monocyte/macrophage cells.

Background: In immunologic research, mice have advantages over other animals, such as low costs, easy handling, suitable life cycle, and adequate laboratory resources. However, vascularized composite allotransplantation surgery using mice is not popular, partly because of technical difficulties and high mortality rates. The authors' goal was to demonstrate a face transplantation model in mice that includes skin, mandible, and oral mucosa., Methods: The authors developed a new syngeneic face transplantation model composed of skin, mandible, teeth, and oral mucosa in C57BL/6 mice. The following assessment included measuring the length of the right incisor on the transplanted mandibles, computed tomographic scan in one mouse for mandibular structure evaluation, and histologic examination of different tissue samples in another mouse for viability evaluation., Results: The authors performed five consecutive transplantations. The donor vessels were the common carotid artery (approximately equal to 0.4 mm) and the anterior facial vein (approximately equal to 0.2 mm), and the recipients were the common carotid artery and the posterior facial vein (approximately equal to 0.4 mm). The mean operative time was 80 minutes for the donor and 123 minutes for the recipient. There were neither flap failures nor animal deaths. The follow-up was 6 months. The right incisor of the transplant grew at different rates in all cases. Histologic samples showed viability in all tissues, including mandibular bone marrow. Computed tomography demonstrated normal structure of the transplanted bone., Conclusion: The authors' syngeneic partial face transplantation model in mice, which included skin, oral mucosa, and mandible with teeth, should be useful for future face allotransplantation research, as the myriad of tissues it provides, of different immunomodulatory functions, is similar to that in the clinical scenario.