Sequential free fibula transfers: Quality of life and systematic review.

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.

Quality-of-Life Outcomes in Oral Cancer Patients Reconstructed With Double Free Flaps: A Preoperative and Postoperative Assessment.

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.

Evaluating Head and Neck Reconstruction Outcomes Proves Difficult-Seeking Improvement in Reporting.

This Viewpoint advocates for the improvement of the quality of head and neck reconstruction studies through accurate depictions of the defect and reconstruction performed.

Evolution of free flap reconstruction in the upper extremity: perspective from a tertiary plastic and reconstructive institution.

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.

Foot Plantar Pressure Profile Alteration after Microsurgical Great Toe-to-thumb Transfer.

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.

Fibula Jaw-during-Admission.

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.

Toward transplantation tolerance with adipose tissue-derived therapeutics.

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.

Quantization of extraoral free flap monitoring for venous congestion with deep learning integrated iOS applications on smartphones: a diagnostic study.

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.

IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism.

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.

Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities.

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.

Reciprocal Donor-Recipient Strain Combinations Present Different Vascularized Composite Allotransplantation Outcomes in Rodent Models.

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.

Asian Upper Blepharoplasty with the Hinge Technique.

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 .

The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism.

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.

Reconstruction of mandibular defects involving the central segment with fibula osteoseptocutaneous free flap following ameloblastoma resection: Patient-reported outcomes.

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 ±â€¯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.

The Anterolateral Thigh Perforator Flap: Its Expanding Role in Lower Extremity Reconstruction.

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.

Fibula Jaw-in-a-Day with Minimal Computer-Aided Design and Manufacturing: Maximizing Efficiency, Cost-Effectiveness, Intraoperative Flexibility, and Quality.

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.

The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation.

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 × 108 or 3 × 107 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.