Publications by authors named "Cheng-Hung Lin"

92 Publications

Formation of three-dimensional bicontinuous structures via molten salt dealloying studied in real-time by in situ synchrotron X-ray nano-tomography.

Nat Commun 2021 Jun 9;12(1):3441. Epub 2021 Jun 9.

Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY, USA.

Three-dimensional bicontinuous porous materials formed by dealloying contribute significantly to various applications including catalysis, sensor development and energy storage. This work studies a method of molten salt dealloying via real-time in situ synchrotron three-dimensional X-ray nano-tomography. Quantification of morphological parameters determined that long-range diffusion is the rate-determining step for the dealloying process. The subsequent coarsening rate was primarily surface diffusion controlled, with Rayleigh instability leading to ligament pinch-off and creating isolated bubbles in ligaments, while bulk diffusion leads to a slight densification. Chemical environments characterized by X-ray absorption near edge structure spectroscopic imaging show that molten salt dealloying prevents surface oxidation of the metal. In this work, gaining a fundamental mechanistic understanding of the molten salt dealloying process in forming porous structures provides a nontoxic, tunable dealloying technique and has important implications for molten salt corrosion processes, which is one of the major challenges in molten salt reactors and concentrated solar power plants.
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http://dx.doi.org/10.1038/s41467-021-23598-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190292PMC
June 2021

Automatic colonic polyp detection using integration of modified deep residual convolutional neural network and ensemble learning approaches.

Comput Methods Programs Biomed 2021 Jul 14;206:106114. Epub 2021 Apr 14.

Department of Electrical and Electronic Engineering, Universiti Teknologi PETRONAS, 32610 Seri Iskandar, Perak, Malaysia. Electronic address:

Background And Objective: The increased incidence of colorectal cancer (CRC) and its mortality rate have attracted interest in the use of artificial intelligence (AI) based computer-aided diagnosis (CAD) tools to detect polyps at an early stage. Although these CAD tools have thus far achieved a good accuracy level to detect polyps, they still have room to improve further (e.g. sensitivity). Therefore, a new CAD tool is developed in this study to detect colonic polyps accurately.

Methods: In this paper, we propose a novel approach to distinguish colonic polyps by integrating several techniques, including a modified deep residual network, principal component analysis and AdaBoost ensemble learning. A powerful deep residual network architecture, ResNet-50, was investigated to reduce the computational time by altering its architecture. To keep the interference to a minimum, median filter, image thresholding, contrast enhancement, and normalisation techniques were exploited on the endoscopic images to train the classification model. Three publicly available datasets, i.e., Kvasir, ETIS-LaribPolypDB, and CVC-ClinicDB, were merged to train the model, which included images with and without polyps.

Results: The proposed approach trained with a combination of three datasets achieved Matthews Correlation Coefficient (MCC) of 0.9819 with accuracy, sensitivity, precision, and specificity of 99.10%, 98.82%, 99.37%, and 99.38%, respectively.

Conclusions: These results show that our method could repeatedly classify endoscopic images automatically and could be used to effectively develop computer-aided diagnostic tools for early CRC detection.
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http://dx.doi.org/10.1016/j.cmpb.2021.106114DOI Listing
July 2021

A 19-Year Experience With Clavicular Defects: An Algorithm for Flap Selection and Surgical Outcomes.

Ann Plast Surg 2021 05;86(5):562-567

Background: The clavicle contributes to the stability and functional integrity of the shoulder. Clavicle bone defects are uncommon, and the strategy for their management is variable.

Method: Six patients presented with clavicle bone defects. The causes were as follows: traumatic defects (2 patients), electric injury (1 patient), osteoradionecrosis (2 patients), and nonunion (1 patient). One patient had upper limb palsy for 40 years, and another had posttraumatic shoulder function impairment. A pedicled pectoralis major myocutaneous flap was used for the patient with a dysfunctional limb, and 5 bone flaps (3 free fibular flaps, 1 free iliac flap, and 1 pedicled rib flap) were used for reconstruction in the other patients.

Result: All flaps (2 pedicled flaps and 4 free flaps) were successfully used for wound repair; the pedicled rib flap demonstrated partial marginal necrosis, and the free fibular flap required reexploration for venous kinking. Five functionally impaired upper limbs showed functional improvements postoperatively.

Conclusion: For functionless composite clavicles and soft tissue defects, a soft tissue flap will be required for wound repair. A bone flap, especially a fibular flap, is required for the upper limb to show functional recovery. The variety of flaps will be planned according to the defect size comparison between the bone and soft tissue, and ipsilateral upper limb function, and a proposed algorithm will be discussed.
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http://dx.doi.org/10.1097/SAP.0000000000002547DOI Listing
May 2021

The Medial Sural Artery Perforator Flap in Lower Extremity Reconstruction.

Clin Plast Surg 2021 Apr 5;48(2):249-257. Epub 2021 Feb 5.

Department of Plastic and Reconstructive Surgery, Chiayi Chang Gung Memorial Hospital, 6, Sec. West, Chia-Pu Road, Putzu City, Chiayi County, Taiwan.

Medial sural artery perforator (MSAP) flap is a thin, pliable, and versatile flap. It is a fasciocutaneous flap with chimeric design capacity. The donor site permits the synchronous harvesting of nonvascularized tendons and nerves. Free MSAP flap is suitable for foot, ankle, and distal one-third of the leg reconstructions. Pedicled MSAP flap is an alternative flap for knee and proximal two-thirds of leg defects, covering classical lower limb reconstruction territories of soleus, medial, and lateral gastrocnemius muscle flap. Computed tomography angiography, indocyanine green, and endoscopic-assist dissection enhances MSAP flap surgical planning and reduces its technical adversities and complications.
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http://dx.doi.org/10.1016/j.cps.2021.01.003DOI Listing
April 2021

Sonoelastography in the Diagnosis of Carpal Tunnel Syndrome: A Systematic Review of Diagnostic Values Compared With the Normative Population.

Ann Plast Surg 2021 03;86(3S Suppl 2):S299-S311

Background: Sonoelastography (SEL) is widely used for assessing tissue stiffness and pathophysiology. It has also been used to diagnose carpal tunnel syndrome (CTS). However, the current criteria to diagnose CTS in SEL are diverse. The aim of this study was to systematically review the literature and assess the diagnostic value of SEL for CTS.

Methods: A literature review was performed using MEDLINE (PubMed), EMBASE, and the Cochrane Collaboration Library for primary research articles using the keywords sonoelastography and carpal tunnel syndrome. Data related to diagnostic and cutoff value were extracted. Bias assessment was performed.

Results: A total of 121 publications were reviewed. Nineteen primary case series met the inclusion criteria and were selected for full analysis. Different diagnostic approaches were identified, with units/expressions including kilopascals, conduct velocity, and strain ratio. The kilopascals and conduct velocity were measured using shear wave elastography, whereas strain ratio was calculated by relative compression quantification. A mean shear modulus cutoff value from 38.25 to 86 kPa and an acoustic radiation force impulse cutoff value of 3.0 to 3.23 m/s were used to diagnose CTS. Eight articles reported strain ratio between the median nerve and nearby tissues with diverse results due to different reference points. The other 3 additional diagnostic values were reported.

Conclusions: Sonoelastography is a useful noninvasive and promising modality to diagnose CTS. It may reflect both the condition of soft tissue scarring and quantitative values for CTS and median nerve stiffness. A diversity of examination values was found in different modalities. A high level of evidence was absent.
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http://dx.doi.org/10.1097/SAP.0000000000002686DOI Listing
March 2021

End-to-Side Anterior Interosseous Nerve Transfer: A Valuable Alternative for Traumatic High Ulnar Nerve Palsy.

Ann Plast Surg 2021 02;86(2S Suppl 1):S102-S107

From the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan.

Background: The prognosis of high ulnar nerve injury is poor despite nerve repair or grafting. Anterior interosseous nerve (AIN) transfers provide a satisfactory recovery. However, the efficacy of end-to-side (ETS) AIN transfer and optimal timing in Sunderland grade IV/V of high ulnar nerve injury is lacking.

Objective: The goals were to compare the outcomes of high ulnar nerve injury managed with ETS AIN transfers with those managed with conventional procedures (nerve repair or graft only) and identify differences between early and delayed transfers.

Methods: Patients with isolated high ulnar nerve injury (Sunderland grade IV/V) from 2010 to 2017 were recruited. Patients with conventional treatments and AIN transfers were designated as the control and AIN groups, respectively. Early transfer was defined as the AIN transfer performed within 8 weeks postinjury. Outcomes were measured and analyzed by the British Medical Research Council (BMRC) score, grip strength, and pinch strength.

Results: A total of 24 patients with high ulnar nerve injury (Sunderland grade IV/V) were included. There were 11 and 13 patients in the control and AIN groups, respectively. In univariate analysis, both early and delayed AIN transfers demonstrated significantly better motor recovery among BMRC score and strength of grip and pinch at 12 months (P < 0.05). No statistical significance was found between early and delayed transfer. In multivariate analysis, both early and delayed transfers were regarded as strong and independent factors for motor recovery of ulnar nerve. Compared with the control, early [odds ratio (OR), 1.83; P < 0.001] and delayed (OR, 1.59; P < 0.001) transfers showed significant improvement with regard to BMRC scores. The pinch strength in early (OR, 31.68; P < 0.001) and delayed (OR, 26.45; P < 0.001) transfers was also significantly better.

Conclusion: The ETS AIN transfer, in either early or delayed fashion, significantly improved intrinsic motor recovery in high ulnar nerve injuries classified as Sunderland grade IV/V. The early transfer group demonstrated a trend toward better functional recovery with less downtime.
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http://dx.doi.org/10.1097/SAP.0000000000002657DOI Listing
February 2021

Unraveling the Crucial Roles of FoxP3+ Regulatory T Cells in Vascularized Composite Allograft Tolerance Induction and Maintenance.

Transplantation 2021 06;105(6):1238-1249

Department of Plastic and Reconstructive Surgery, Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Gueishan, Taiwan.

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.
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http://dx.doi.org/10.1097/TP.0000000000003509DOI Listing
June 2021

Nano- to microscale three-dimensional morphology relevant to transport properties in reactive porous composite paint films.

Sci Rep 2020 Oct 27;10(1):18320. Epub 2020 Oct 27.

Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY, 11794, USA.

The quantitative evaluation of the three-dimensional (3D) morphology of porous composite materials is important for understanding mass transport phenomena, which further impact their functionalities and durability. Reactive porous paint materials are composites in nature and widely used in arts and technological applications. In artistic oil paintings, ambient moisture and water and organic solvents used in conservation treatments are known to trigger multiple physical and chemical degradation processes; however, there is no complete physical model that can quantitatively describe their transport in the paint films. In the present study, model oil paints with lead white (2PbCO·Pb(OH)) and zinc white (ZnO) pigments, which are frequently found in artistic oil paintings and are associated with the widespread heavy metal soap deterioration, were studied using synchrotron X-ray nano-tomography and unilateral nuclear magnetic resonance. This study aims to establish a relationship among the paints' compositions, the 3D morphological properties and degradation. This connection is crucial for establishing reliable models that can predict transport properties of solvents used in conservation treatments and of species involved in deterioration reactions, such as soap formation.
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http://dx.doi.org/10.1038/s41598-020-75040-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591493PMC
October 2020

Does muscle improve validated outcome measures in open tibial fractures? New insights from a cohort study of the anterolateral thigh flap (ALT) versus ALT-Vastus lateralis flaps.

J Plast Reconstr Aesthet Surg 2021 02 15;74(2):268-276. Epub 2020 Sep 15.

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan. Electronic address:

The benefits of the muscle in open lower limb fractures remain to be determined. This study compared statistically equivalent groups of open tibial fractures treated by free anterolateral thigh (ALT) flaps or ALT flaps incorporating muscle (ALT-Vastus lateralis/ALT- VL). Method and Results: Chang Gung Memorial Hospital, Taiwan, 2004-2008, 49 free flaps in open lower limb fractures (38 open tibial) were specifically reconstructed with free ALT or ALT-VL flaps. Risk factors for non-union: equivalent between the two groups, with no differences in smoking, steroids, diabetes, time to flap and the AO classification of soft tissue and bone injury. Comparison of union rates: no difference was noted between groups in the Radiographic Union Score in Tibial Fractures (RUST) at 3, 6, 9 and 12 months. The only factor significantly associated with non-union was presence of a SPRINT trial defined 'critical' bone defect with odds ratio 14.4 (95% CI 1.36 - 131.5), with no association with AO bone classification, flap type, comorbidity or flap size. Patient-reported outcomes: the ALT-VL group showed improved patient satisfaction (p = 0.01, Cohen's d = 1.1). Functional outcomes (Enneking score) were not statistically significant, but the ALT-VL group trended towards significance in function and skin quality domains. Conclusions: Based on the results of this study, one can conclude that the degree of bone injury (specifically a 'critical' defect) is of greater relevance than flap choice with regard to fracture consolidation. Muscle does not result in improvements to union, the speed of union or deep infection. However, better PROMs may be related to the inclusion of the muscle around the fracture site.
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http://dx.doi.org/10.1016/j.bjps.2020.08.097DOI Listing
February 2021

The Medial Sural Artery Perforator Flap: Lessons Learned from 200 Consecutive Cases.

Plast Reconstr Surg 2020 11;146(5):630e-641e

From the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University.

Background: The medial sural artery perforator flap is a versatile option in reconstructive microsurgery. However, most reports of this flap have been limited by sample size. This study reviews the experience of a single large-volume center using the medial sural artery perforator flap and its variants for a variety of reconstructive purposes.

Methods: A retrospective review of all patients who received the medial sural artery perforator flap reconstruction between March of 2006 and July of 2014 was performed.

Results: Two-hundred medial sural artery perforator flaps were used at three anatomical regions: head and neck (n = 129), upper extremity (n = 47), and lower extremity (n = 24). Flaps were transferred as free (n = 189) and pedicled (n = 11). Overall flap survival was 96 percent. Flap variants used included chimeric flap (n = 11) and dual skin paddle (n = 2). Plantaris tendon and saphenous/sural nerve graft were harvested in conjunction in 20 and seven patients, respectively. In 5 percent of the cases harvested in the conventional manner, a reliable perforator could not be found.

Conclusions: The medial sural artery perforator flap is a reliable, alternative workhorse flap for nearly any small- to medium-size defect. It can be harvested as free or pedicled and the option to include multiple tissue components further expands its versatility.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000007282DOI Listing
November 2020

Iterative Pose Refinement for Object Pose Estimation Based on RGBD Data.

Sensors (Basel) 2020 Jul 24;20(15). Epub 2020 Jul 24.

Department of Electrical Engineering, National Taiwan Normal University, Taipei 106, Taiwan.

Accurate estimation of 3D object pose is highly desirable in a wide range of applications, such as robotics and augmented reality. Although significant advancement has been made for pose estimation, there is room for further improvement. Recent pose estimation systems utilize an iterative refinement process to revise the predicted pose to obtain a better final output. However, such refinement process only takes account of geometric features for pose revision during the iteration. Motivated by this approach, this paper designs a novel iterative refinement process that deals with both color and geometric features for object pose refinement. Experiments show that the proposed method is able to reach 94.74% and 93.2% in ADD(-S) metric with only 2 iterations, outperforming the state-of-the-art methods on the LINEMOD and YCB-Video datasets, respectively.
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http://dx.doi.org/10.3390/s20154114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436036PMC
July 2020

Diboron-Based Delayed Fluorescent Emitters with Orange-to-Red Emission and Superior Organic Light-Emitting Diode Efficiency.

ACS Appl Mater Interfaces 2020 May 7;12(20):23199-23206. Epub 2020 May 7.

Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.

For the application of organic light-emitting diodes (OLEDs) in lighting and panels, the basic requirement is to include a full spectrum color range. Compared with the development of blue and green luminophores in thermally activated delayed fluorescence (TADF) technology, the progress of orange-to-red materials is slow and needs further investigation. In this study, three diboron compound-based materials, dPhADBA, dmAcDBA, and SpAcDBA, were designed and synthesized by nucleophilic arylation of three amine donors on 9,10-diboraanthracene (DBA) in a two-step reaction. With increasing electron-donating ability, they show orange-to-red emission with TADF characteristics. The electroluminescence of these diboron compounds exhibits emissions λ at 613, 583, and 567 nm for dPhADBA, dmAcDBA, and SpAcDBA, respectively. It is noteworthy that the rod-like D-A-D structures can achieve high horizontal ratios (84-86%) and outstanding device performance for orange-to-red TADF OLEDs: the highest external quantum efficiencies for dPhADBA, dmAcDBA, and SpAcDBA are 11.1 ± 0.5, 24.9 ± 0.5, and 30.0 ± 0.8%, respectively. Therefore, these diboron-based molecules offer a promising avenue for the design of orange-to-red TADF emitters and the development of highly efficient orange-to-red OLEDs.
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http://dx.doi.org/10.1021/acsami.0c03711DOI Listing
May 2020

Necrotizing fasciitis of the entire head and neck: Literature review and case report.

Biomed J 2020 02 27;43(1):94-98. Epub 2020 Feb 27.

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Necrotizing fasciitis (NF) is uncommon but potentially lethal when it is associated with systemic disorders. We report a case of odontogenic NF in a patient with uncontrolled diabetes mellitus. The patient was referred on day 10 since the onset of odontogenic NF. Protective tracheostomy, local facial-cervical fasciotomy were conducted and broadspectrum antibiotics were given, subsequent serial surgical drainage and debridement were performed in theater. Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia were isolated. Five staged debridements were performed to the targeted anatomic regions thus reducing surgical time and blood loss. The patient survived the acute infection and received subsequent reconstruction. Cervical NF with descending mediastinitis and periorbital NF is associated with high mortality rates. This is the only known report of an adult who survived NF affecting entire scalp, periorbital, cervical, and thoracic region. Early diagnosis and staged surgical planning minimize morbidity and mortality from NF.
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http://dx.doi.org/10.1016/j.bj.2019.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090320PMC
February 2020

Systems-level investigation of aqueous batteries for understanding the benefit of water-in-salt electrolyte by synchrotron nanoimaging.

Sci Adv 2020 Mar 6;6(10):eaay7129. Epub 2020 Mar 6.

Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.

Water-in-salt (WIS) electrolytes provide a promising path toward aqueous battery systems with enlarged operating voltage windows for better safety and environmental sustainability. In this work, a new electrode couple, LiVO-LiMnO, for aqueous Li-ion batteries is investigated to understand the mechanism by which the WIS electrolyte improves the cycling stability at an extended voltage window. Operando synchrotron transmission x-ray microscopy on the LiMnO cathode reveals that the WIS electrolyte suppresses the mechanical damage to the electrode network and dissolution of the electrode particles, in addition to delaying the water decomposition process. Because the viscosity of WIS is notably higher, the reaction heterogeneity of the electrodes is quantified with x-ray absorption spectroscopic imaging, visualizing the kinetic limitations of the WIS electrolyte. This work furthers the mechanistic understanding of electrode-WIS electrolyte interactions and paves the way to explore the strategy to mitigate their possible kinetic limitations in three-dimensional architectures.
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http://dx.doi.org/10.1126/sciadv.aay7129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060054PMC
March 2020

Predicting Outcomes of Rat Vascularized Composite Allotransplants through Quantitative Measurement of Chimerism with PCR-Amplified Short Tandem Repeat.

J Immunol Res 2020 4;2020:9243531. Epub 2020 Feb 4.

Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Kueishan Taoyuan 333, Taiwan.

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 Chimerism) 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.
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http://dx.doi.org/10.1155/2020/9243531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024101PMC
October 2020

Designing Multiscale Porous Metal by Simple Dealloying with 3D Morphological Evolution Mechanism Revealed via X-ray Nano-tomography.

ACS Appl Mater Interfaces 2020 Jan 2;12(2):2793-2804. Epub 2020 Jan 2.

Department of Materials Science and Chemical Engineering , Stony Brook University , Stony Brook , New York 11794 , United States.

Designing materials with multiscale, hierarchical structure is critical to drive the advancement of new technology. Specifically, porous metals with multiscale porosity from nanometer to micrometer sizes would lead to enhanced physical and chemical properties-the micron-sized pores can increase the effective diffusivity of ion transport within the porous media, and the nano-sized pores provide high specific surface area, enabling functionalities that are unique to nanoporous metals. A new ternary precursor alloy selection concept utilizing the different mixing enthalpies is demonstrated in this work for the design of multiscale, bimodal porous copper from a simple, one-step dealloying of Cu-Fe-Al ternary alloy. The nanoporosity in the bimodal porous structure is formed from dealloying of the Cu-rich phase, whereas the microporosity is controlled by dissolving the Fe-rich phase, determined by both the initial Fe particle size and sintering profile. In addition to advancing the materials design method, the multiscale pore formation during dealloying was directly visualized and quantified via an interrupted in situ synchrotron X-ray nano-tomography. The 3D morphological analysis on tortuosity showed that the presence of the microporosity can compensate the increase of the diffusion path length due to nanoporosity, which facilitates diffusion within the porous structure. Overall the focus of the work is to introduce a new strategy to design multiscale porous metals with enhanced transport properties, and sheds light on the fundamental mechanisms on the 3D morphological evolution of the system using advanced synchrotron X-ray nano-tomography for future materials development and applications.
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http://dx.doi.org/10.1021/acsami.9b16392DOI Listing
January 2020

Perfusion dynamics of the medial sural artery perforator (MSAP) flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI): a clinical study.

J Plast Surg Hand Surg 2020 Apr 14;54(2):112-119. Epub 2019 Dec 14.

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taiwan.

Perforator flaps are a mainstay in reconstructive surgical practice but are limited by complications, including flap failure, resulting from flap hypoperfusion. This study aimed to characterize the early post-operative perfusion dynamics of the medial sural artery perforator (MSAP) flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI). 12 patients, recruited between 2014 and 2015, with lower extremity reconstructions using free MSAP flaps were assessed for perfusion using a hand-held colour Doppler ultrasound device on days 1, 3, and 5 post-operatively. Perfusion at four distinct zones was assessed; whole flap, control zone, perforator zone, and distal zone, by a single operator using a standardized technique. The perforator zone was noted to have the highest relative perfusion of all zones measured across all post-operative days, and this was correlated with whole flap perfusion ( 0.82,  = 0.002). No significant perfusion differences were found within any of the zones over the 5-day period. The perfusion at the distal zone was not found to correlate with either the perforator zone perfusion, flap length, flap length to width ratio or smoking status ( > 0.05). Perfusion of the MSAP flap can adequately be monitored using LDPI at any point throughout the flap, though is highest at the perforator zone, and remains constant in the early post-operative period.
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http://dx.doi.org/10.1080/2000656X.2019.1703191DOI Listing
April 2020

Attitudes of Hand Surgeons and Hand Reconstruction Patients Toward Hand Allotransplantation in Taiwan.

Ann Plast Surg 2020 01;84(1S Suppl 1):S107-S111

From the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan.

Background: Recent advances in immunosuppressive protocols have increasingly made hand allotransplantation a realistic reconstructive option with more than 100 cases performed worldwide. While attitudes toward allotransplantation have been assessed for North American surgeons and patients alike, similar assessments have previously remained unconducted in Asia in general and Taiwan in specific. This study examines the perceptions of both Taiwanese hand surgeons and hand reconstruction patients.

Methods: An email-based survey was sent to all active members of the Taiwanese Society for Surgery of the Hand. Surgeon training backgrounds and practice profiles were gathered as well as current beliefs on indications, risks, ethicality, priority of psychosocial issues, and obstacles to implementation. Patients receiving rehabilitation at Chang Gung Memorial Hospital Linkou after severe upper extremity injuries were invited to complete a patient survey. Demographics, injury characteristics, understanding of allotransplantation and immunosuppression, willingness to donate, and willingness to receive transplantation were assessed.

Results: Forty-four hand surgeons responded (24.3% response rate). The majority (61.4%) considered hand allotransplantation to be a high-risk operation, although 40% supported the development of hand allotransplantation under current techniques and immunosuppression. Bilateral hands loss was the most commonly accepted indication for transplant (90.9%), whereas dominant hand loss was less frequently accepted (43.2%). Treatment compliance and functional outcomes were the most frequent psychosocial issues of concern regarding patient counseling. Patient respondents were mostly in the fifth decade of life (29.5%) with at least a high school education (75.0%). Most were aware of the feasibility of hand transplantation (68.2%). Patients were more likely than surgeons to consider nondominant hand, multiple-digit, and thumb-only amputations as indications for transplantation. Functional outcomes and financial considerations were the most frequent patient concerns.

Conclusions: This study indicates there is support for hand allotransplantation as a solution for limb loss in both hand surgeons and hand patients in Taiwan. This study adds to the lack of knowledge regarding surgeon and patient attitudes toward allotransplantation in Asia, although further work is required to assess the willingness of broader Taiwanese medical to refer candidates and for the general population to donate.
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http://dx.doi.org/10.1097/SAP.0000000000002171DOI Listing
January 2020

Flaps Based on Perforators of the Digital Artery.

Hand Clin 2020 02;36(1):57-62

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing Street, Guishan District, Taoyuan City 333, Taiwan.

This review article summarizes the various types of digital artery perforator flaps used in digit reconstruction. The indications for use of digital artery perforator flaps and the preferred approach for reconstructing fingertip defects are explained in this article. Recent updates in digital artery perforator anatomy in the finger, techniques for flap harvest, and inset as well as a delayed approach to using digital perforator flaps in finger reconstruction are discussed.
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http://dx.doi.org/10.1016/j.hcl.2019.08.007DOI Listing
February 2020

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

Cell Mol Immunol 2021 02 21;18(2):363-373. Epub 2019 Nov 21.

Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

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 or 3 × 10 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.
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http://dx.doi.org/10.1038/s41423-019-0325-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027407PMC
February 2021

Anterolateral thigh free flaps for the reconstruction of scalp angiosarcoma - 18-year experience in Chang Gung memorial hospital.

J Plast Reconstr Aesthet Surg 2019 Dec 8;72(12):1900-1908. Epub 2019 Aug 8.

Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chia-Yi, Taiwan. Electronic address:

Background: Scalp angiosarcoma is a rare and highly aggressive cutaneous malignancy with poor prognosis and high recurrence rate. Multimodality approach is currently the treatment protocol for resectable angiosarcoma, including wide local excision and postoperative radiation. This single-institution study reviews the 18-year experience of the surgical treatment of scalp angiosarcomas.

Methods: A retrospective chart review was performed on patients with scalp angiosarcoma who received wide local excision and free flap reconstruction from 2001 to 2018. The type of free flap, safety margin, outer cortex burring, and dose for radiation were recorded. Kaplan-Meier plots were computed.

Results: Eight male patients (mean age of 74.4 years old) were enrolled in the series. Tumor sizes ranged from 3 × 3 to 8 × 13 cm. All patients underwent wide local excision and outer cortex burring (cortical curettage). Seven (87.5%) scalp defects were reconstructed with anterolateral thigh free flap. All patients received adjuvant radiation therapy for tumor bed and margins. Chemotherapy was adopted for the management of local recurrence (37.5%) or distant metastasis (37.5%). The 2-year and 5-year survival rates are 72.9% and 38.9%, respectively, and 1-year and 2-year disease-free rates are 37.5% each.

Conclusion: Scalp angiosarcoma is a rare and highly aggressive cutaneous malignancy with poor prognosis. Anterolateral thigh free flap is a good reconstructive option due to its ability to cover large cutaneous defects with minimal need for skin grafting. Multimodal treatment protocol, including wide local excision with cortical curettage, and adjuvant radiation (regular basis) and chemotherapy (local recurrence or distant metastasis) may offer improved 1-year survival rate (100%).
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http://dx.doi.org/10.1016/j.bjps.2019.07.024DOI Listing
December 2019

A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy.

Pharmaceutics 2019 Aug 14;11(8). Epub 2019 Aug 14.

Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.

Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P-Lys-Ala-PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy.
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http://dx.doi.org/10.3390/pharmaceutics11080413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723608PMC
August 2019

Unilateral Pedicled Pectoralis Major Harvested by Endoscopic-Assisted Method Achieves Adequate Management of Sternal Infection and Mediastinitis.

J Reconstr Microsurg 2019 Nov 30;35(9):705-712. Epub 2019 Jul 30.

Department of Cardiovascular Surgery, Chang Gung Memorial Hospital in Linko, Chang Gung University, Taoyuan, Taiwan.

Background:  Bilateral PM muscles or combination with rectus abdominis or omentum are commonly used for upper and lower sternal wound infections. Unilateral PM harvesting using endoscopic-assisted method may have a simple, safe, and reliable entire muscle harvesting with comparable result of less donor-site violation.

Methods:  A retrospective review was performed from 2003 till 2015 on 38 patients referred to a single plastic surgeon for treatment of sternal wound infection following median sternotomy for cardiovascular surgery. After the humerus insertion of PM was cut with the assistance of endoscope visualization, all the other PM insertions on the sternum, rib, and clavicle were divided, the unilateral pedicled PM can be advanced approximately 10 cm to cover the cephalad and caudal sternum, and fill the retrosternal mediastinum.

Results:  Four re-explorations in three patients for postoperative hematoma occurred. No early recurrent infection for wound dehiscence experienced. Three patients died of multiple organs failures as 30-day mortality. Two patients underwent late recurrent infections; one patient had twice wire infection removals at 4 and 6 months after transfer, and the other had another PM for rib osteomyelitis in 3 years.

Conclusion:  Unilateral PM transfer is justified to provide a simple, reliable, straightforward procedure for sternal infection management and mediastinal obliteration without violation of second flap in compromised patients.
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http://dx.doi.org/10.1055/s-0039-1695089DOI Listing
November 2019

Early recovery of neuronal functioning in the sensory cortex after nerve reconstruction surgery.

Restor Neurol Neurosci 2019 ;37(4):409-419

Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan.

Background: Nerve reconstructive surgery induces a transient loss and a prolonged and a gradual return of sensory inputs to the brain. It is unknown whether, following this massive peripheral denervation, the brain will experience a prolonged period of severe, intrinsic dysfunction.

Objective: We aim to investigate the mechanisms of return of processing function in cortical neurons.

Methods: We used the whisker model in rats to evaluate the functional recovery in the somatosensory cortex after a nerve reconstruction surgery. Multi-unit recording in the barrel cortex was performed in lightly anesthetized rats while their whiskers were stimulated by a whisker stimulator.

Results: We observed a loss of neuronal responses to whisker stimulation 1 week after surgery, which started to recover 2 weeks after surgery. Following the surgery, only 11.8% of units had principle whiskers (PWs) returned to their original status while 17.7% had PWs different from their original status, indicating the effect of aberrant reinnervation on the whisker response map.

Conclusions: Robust neuronal responses to sensory stimulation even when only sparse sensory inputs are available in the early recovery phase. During this phase, aberrant reinnervation induces disorganized whisker tuning, a finding that might be account for the hypoesthesia and paresthesia during early recovery after nerve reconstruction.
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http://dx.doi.org/10.3233/RNN-190914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700653PMC
April 2020

A New Face Subunit Transplant Model in Mice, Containing Skin, Mandible, and Oral Mucosa for Future Face Vascularized Composite Allotransplantation Studies.

Plast Reconstr Surg 2019 07;144(1):115-123

From the Department of Plastic and Reconstructive Surgery, the Center for Vascularized Composite Allotransplantation, the Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College; St Andrew's Center for Burns and Plastic Surgery; and the Department of Plastic Surgery, IPS Universitaria/León XIII Hospital, University of Antioquia.

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.
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http://dx.doi.org/10.1097/PRS.0000000000005774DOI Listing
July 2019

Patient-Reported Outcome Measures for Toe-to-Hand Transfer: A Prospective Longitudinal Study.

Plast Reconstr Surg 2019 Apr;143(4):1122-1132

From the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University.

Background: Patient-reported outcome measures are an important metric in evaluating treatment efficacy of reconstructive surgery. Toe-to-hand transfer can restore vital prehensile function; however, this surgery is complex, extensive rehabilitation is required, and there are concerns about donor-site morbidity. This study longitudinally explores the benefits of this procedure, from the patient's perspective, using patient-reported outcome measures.

Methods: Twenty-three patients who underwent free toe-to-hand transfers from 2012 to 2015 were evaluated preoperatively and postoperatively using the following validated questionnaires: the Michigan Hand Outcomes Questionnaire, the 36-Item Short-Form Health Survey, and the Lower Limb Outcomes Questionnaire. Subgroup analysis was performed between dominant and nondominant reconstructed hands.

Results: Mechanism of injury was crush in 83 percent; the remainder sustained cutting, avulsion, and burn injuries. Thirty-four toes were transferred: nine great toes, 20 second toes, and five third toes. Michigan Hand Outcomes Questionnaire results showed significant improvement in overall activities of daily living, work, aesthetics, and patient satisfaction (p < 0.05). The results of the 36-Item Short-Form Health Survey showed significant improvements in physical and emotional roles (p < 0.05). The Lower Limb Outcomes Questionnaire showed no deterioration of foot function (p = 0.55). Subgroup analysis showed significant improvement in patient-reported outcome measures for patients undergoing dominant hand reconstruction but no difference between thumb reconstruction and finger-only reconstruction.

Conclusions: Patient-reported outcome measures demonstrate the significant utility of toe-to-hand transfer procedures in both functional and psychosocial domains in that there are relatively greater benefits in reconstructing the dominant hand, and that donor-site morbidity is well tolerated.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000005422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438721PMC
April 2019

Rationalizing the Vascular Anatomy for Oblique Osteotomy of the Metatarsal Head during Toe/Joint Transfers of the Metatarsophalangeal Joint.

Plast Reconstr Surg Glob Open 2018 Oct 3;6(10):e1805. Epub 2018 Oct 3.

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung & Taoyuan, Taiwan.

Background: The metatarsophalangeal joint (MTPJ) of the lessor toe has been used to reconstruct the metacarpophalangeal joint. When an oblique osteotomy of the metatarsal head is performed, the orientation of the vascular pedicle is crucial to preserve the blood supply to the MTPJ. This study was conducted to identify the path of the nutrient artery to the MTPJ.

Methods: We reviewed our operative records in consecutive series of 45 patients during toe or joint harvest. Retrograde dissection of the vascular pedicle was performed starting from the distal communicating artery at the first webspace toward the first dorsal metatarsal and first plantar metatarsal arteries. All the vessels related to the MTPJ were explored and ligated if the MTPJ was not included in the flap.

Results: The condylar branches to the proximal phalanx and the metaphyseal branches to the second metatarsus were barely identifiable during the dissections. The articular branch running perpendicularly from the plantar artery toward the plantar surface of MTPJ was verified in all cases. The articular branches originated either from the first plantar metatarsal artery (92.1%) or from the tibial plantar digital artery (7.9%). The external diameter of the articular branches was around 0.5-1 mm. When the articular branch was included and preserved, the metatarsal heads oozed immediately after the flap was reperfused.

Conclusions: The study demonstrated the constant and sizable articular branch of the MTPJ that originates from the plantar artery system. The consistency of the vascular anatomy enables oblique osteotomies of the metatarsal head to be performed without fear of injury to the pedicle.
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http://dx.doi.org/10.1097/GOX.0000000000001805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250473PMC
October 2018

Prognosis of Traumatic Ulnar Nerve Injuries: A Systematic Review.

Ann Plast Surg 2019 01;82(1S Suppl 1):S45-S52

Christine M. Kleinert Institute for Hand and Microsurgery, Louisville, KY.

Ulnar nerve injury (UNI) is not uncommon and often results in incomplete motor recovery after the initial nerve repair and requires secondary functional reconstruction. To clarify the prognosis and predicting factor of UNI, and if it is reasonable to wait after the initial repair, a systematic literature review from PubMed computerized literature database and Google scholar was performed. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist and guidelines were followed to develop the search protocol for this literature review. Two reviewers independently assessed titles, abstracts, and full-text articles, and a third reviewer resolved any disagreements. Seventeen articles with 260 cases were found with sufficient data and enough follow-up. After multiple logistic regression, age, injury level, gap of lesion, and delayed time to surgery were significant prognostic factors in UNI. If considering only high-level injuries (injury at or above proximal forearm), age became the only predicting factor. In cases with likely poor prognosis, their motor recovery tends to be unsatisfactory, and observation for months after the initial repair might not be reasonable. Other surgical interventions such as early nerve transfer may be an option to improve the outcome.
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http://dx.doi.org/10.1097/SAP.0000000000001727DOI Listing
January 2019

Extended Use of Chimeric Medial Sural Artery Perforator Flap for 3-Dimensional Defect Reconstruction.

Ann Plast Surg 2019 01;82(1S Suppl 1):S86-S94

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chiayi Branch, Taiwan.

Background: The medial sural artery perforator (MSAP) flap has become increasingly popular because it is thin and pliable for small to moderate defect soft tissue reconstruction. Furthermore, chimeric MSAP flap, which includes a skin paddle and a separated piece of medial gastrocnemius muscle, allowed more freedom for flap insetting, especially in 3-dimensional defect reconstruction. Here we describe our experience regarding this clinical application.

Patients And Methods: From 2007 to 2016, 14 male patients (average age, 46.9 ± 14.4 years) who received either a free or pedicled chimeric MSAP flap were included. Of these 14 patients, 7 received this flap for reconstruction in the head and neck, 2 in the upper extremities, and 5 in the lower extremities. Demographic data were collected and analyzed, and a literature review was performed.

Results: Ten patients received free chimeric MSAP flap, and 4 received the pedicled type. Thirteen of the 14 flaps (92.6%) survived, and 1 failed 2 days later owing to venous insufficiency. Venous congestion-related partial loss occurred in another case.

Conclusions: The chimeric MSAP flap is a good alternative for deep space obliteration or reconstruction of adjacent but separate defects in both free and pedicled flap design. Donor site morbidity is limited. However, the perforator needs to be mobilized carefully to prevent postoperative venous compromise.
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http://dx.doi.org/10.1097/SAP.0000000000001697DOI Listing
January 2019

Bioimaging of alloantigen-stimulated regulatory T cells in rat vascularized composite allotransplantation.

PLoS One 2018 7;13(9):e0203624. Epub 2018 Sep 7.

Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan, Taiwan.

Background: Tipping the balance toward regulatory T cells (Tregs) through adoptive cell therapy has shown promise to induce transplantation tolerance. Although such strategy has been explored in many mice organ transplantation studies, less knowledge was available in rat systems. Furthermore, the behaviors of the transferred cells have not been well studied in real-time fashion.

Methods: Tregs from naïve LEW rats were purified in two steps with the autoMACS system. Immunosuppression potential of these cells was examined with mixed lymphocyte reaction. Following stimulation by the alloantigen in vitro, the purified Tregs were infused into the recipients of vascularized composite allotransplantation (VCA). Secondary allogeneic skin grafting challenge was performed on the recipients with long-term survived VCA. Live optical imaging was performed to track luciferase-expressing Tregs following infusion to the VCA recipients. Expression of relevant molecules was studied by flow cytometry or quantitative RT-PCR.

Results: Rat Tregs were enriched following two-step cell sorting and showed immunosuppressive capacity. Upon infusion into the VCA recipients that have been treated with antilymphocyte serum and short-term Cyclosporin A, the antigen-stimulated Tregs significantly prolonged VCA survival and induced donor-specific tolerance. Tracking of the infused bioluminescent Tregs showed their specific homing to lymph nodes, and then to the VCAs. Following secondary skin grafting, Tregs specifically gathered at the donor-derived skin that was not rejected by the recipient. The in vivo migratory pattern coincided with the altered expression of cell surface molecules of CD62L, CD103, CD134, and CD278, following donor-antigen stimulation. Elevated expression of CCR4 and CCL22 in allograft may also participate in recruiting Tregs for maintenance of VCA survival and promoting donor-specific tolerance.

Conclusion: Sorted Tregs induced donor-specific tolerance to VCA in rats. Live cell tracking demonstrated that activated CD4+CD25+FoxP3+ Tregs targeted primarily to the lymph nodes and VCA. The Tregs migrated to the secondary grafted donor skin and contributed to the maintenance of donor-specific tolerance. These behaviors were associated with phenotypic changes induced by donor antigen stimulation. Increased expression of CCR4 and CCL22 in VCA skin may also be relevant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203624PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128578PMC
February 2019
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