Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.

OBJECTIVE: Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified. METHODS: This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR-A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC-1) culture to examine the direct effect of TTR-A97S protein on endothelial cells. RESULTS: In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC-1 culture in which the expression of collagen IV was upregulated after exposure to TTR-A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p-selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv. INTERPRETATION: Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration.

Validation of the Efficacy of Ultrasound Speckle Tracking in Measuring Tendon Gliding After Finger Flexor Tendon Repair.

OBJECTIVE: Restricted tendon gliding is commonly observed in patients after finger flexor tendon (FFT) repair. The study described here was aimed at quantifying the amount of FFT gliding to evaluate the recovery of post-operative tendons using a 2-D radiofrequency (RF)-based ultrasound speckle tracking algorithm (UST). METHODS: Ex vivo uniaxial tensile testing of porcine flexor tendons and in vivo isometric testing of human FFT were implemented to verify the efficacy of UST beforehand. The verified UST was then applied to the patients after FFT repair to compare tendon gliding between affected and healthy sides and to investigate its correlation with the joint range of motion (ROM). RESULTS: Excellent validity was confirmed with the average R2 value of 0.98, mean absolute error of 0.15 ± 0.08 mm and mean absolute percentage error of 5.19 ± 2.43% between results from UST and ex vivo testing. The test-retest reliability was verified with good agreement of ICC (0.90). The affected side exhibited less gliding (p = 0.001) and smaller active ROM (p = 0.002) than the healthy side. Meanwhile, a significant correlation between tendon gliding and passive ROM was found only on the healthy side (ρ = 0.711, p = 0.009). CONCLUSION: The present study provides a promising protocol to evaluate post-operative tendon recovery by quantifying the amount of FFT gliding with a validated UST. FFT gliding in patients with different levels of ROM restriction should be further explored for categorizing the severity of tendon adhesion.

Nonpermissive Skin Environment Impairs Nerve Regeneration in Diabetes via Sec31a.

OBJECTIVE: Although the microenvironment for peripheral nerve regeneration is permissive, such a mechanism is defective in diabetes, and the molecular mediators remain elusive. [Correction added on May 11, 2022, after first online publication: In the preceding sentence, "is ok" was changed to "is defective".] This study aimed to (1) investigate the relationship between skin innervation and collagen pathology in diabetic neuropathy and to (2) clarify the molecular alterations that occur in response to hyperglycemia and their effects on axon regeneration. METHODS: We addressed this issue using two complementary systems: (1) human skin from patients with diabetic neuropathy and to (2) a coculture model of human dermal fibroblasts (HDFs) with rat dorsal root ganglia neurons in the context of intrinsic neuronal factor and extrinsic microenvironmental collagen and its biosynthetic pathways. RESULTS: In diabetic neuropathy, the skin innervation of intraepidermal nerve fiber density (IENFd), a measure of sensory nerve degeneration, was reduced with similar expression of a growth associated protein 43, a marker of nerve regeneration. In contrast, the content and packing of collagen in the diabetic skin became more rigid than the control skin. Sec31a, a protein that regulates the collagen biosynthetic pathway, was upregulated and inversely correlated with IENFd. In the cell model, activated HDFs exposed to high-glucose medium enhanced the expression of Sec31a and collagen I through the activation of transforming growth factor ß, a profibrotic molecule. Sec31a upregulation impaired neurite outgrowth. This effect was reversed by silencing Sec31a expression and neurite outgrowth was resumed. INTERPRETATION: The current study provides evidence that Sec31a plays a key role in inhibiting nerve regeneration in diabetic neuropathy. ANN NEUROL 2022;91:821-833.

Cordycepin inhibits the proliferation of malignant peripheral nerve sheath tumor cells through the p53/Sp1/tubulin pathway.

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. In addition to skin pigmentation and cutaneous neurofibroma, some patients developed the plexiform neurofibroma since birth. Plexiform neurofibroma has abundant Schwann cells, fibroblasts, mast cells, blood vessels, and connective tissues, which increases the risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNST is a highly invasive cancer with no effective therapeutic agent. Cordycepin or 3'-deoxyadenosine is an extract from cordyceps militaris, which has been reported as an anti-inflammation and anti-tumor agent. Herein, we evaluated cordycepin's anti-proliferative effect on MPNST cell lines both in vitro and in vivo. Cordycepin inhibited the MPNST cell growth with an arrest of cell cycle at G2/M and S phases. The administration of naringin and pentostatin, inhibitors for adenosine deaminase (ADA), enzyme responsible for cordycepin degradation, did not show a synergistic effect in MPNST cells treated with cordycepin. However, the combined treatment enhanced the decrease of tumors in xenograft mouse model. Immunoblotting showed a decreased level of p53 protein in all MPNST cell lines, but S462TY cells. After cordycepin treatment, the levels of ERK, survivin, pAKT, and Sp1 proteins also decreased. The level of tubulin, but not actin or GAPDH, decreased in a dose-dependent manner. The microtubule network which is composed of tubulins was markedly decomposed in those treated MPNST cells. To elucidate the epigenetic control of transcription, ChIP-qPCR assay of the Sp1 and tubulin promoter regions revealed decreased Sp1 binding. The incorporation of 3'-doexyadenosine is detrimental for the process of poly(A) tail elongation. The poly(A) tail length assay showed the tail length in Sp1 and tubulin transcripts decreased in the treated cells. Nevertheless, the administration of SP1 protein to the treated cells could not rescue them completely. Furthermore, the p53-knocked-down cells (S462TY) where the expression of both p53 and Sp1 was suppressed, were vulnerable to cordycepin. The p53 protein could ameliorate the effect. In summary, cordycepin is effective to inhibit the growth of MPNST, probably through the pathway of p53/Sp1/tubulin.

Resuming Oral Feeding in Patients With Oral Squamous Cell Carcinoma With Free Anterolateral Thigh Flap Reconstruction.

BACKGROUND: Quality of life and functional improvement have emerged as important goals for patients with oncologic disease. For patients with head and neck cancer, free anterolateral thigh (ALT) flaps serve as reliable reconstruction and provide functional restoration. Nevertheless, factors affecting the resumption of oral feeding are rarely described. This study aimed to evaluate and compare the functional outcomes of oral feeding for patients with different oncologic defect patterns and reconstructive ALT flap designs. METHODS: We retrospectively reviewed patients with head and neck cancer undergoing oncologic ablation and free ALT reconstruction between January 2016 and April 2018 at National Taiwan University Hospital. Patients were categorized into 2 groups as through-and-through (T&T) and non-through-and-through (non-T&T) according to the defect pattern. We further subgrouped T&T patients into lip resection/lip sparing according to lip involvement. Reconstructive ALT flaps were of 2 designs, folded (F-ALT) and chimeric (C-ALT). Outcomes of oral feeding were analyzed using descriptive statistics, and differences between groups were compared using the Student t test. RESULTS: We identified 233 patients who received oncologic ablation and free ALT flap reconstruction. There was no significant difference in functional recovery between the T&T and non-T&T groups (81.2% vs 73%, P = 0.137). However, among patients who succeeded in resuming oral feeding, lip-sparing patients had better functional recovery in terms of early oral feeding within 6 months and nasogastric tube removal compared with lip-resection patients (100% vs 83.3%, P = 0.001). Moreover, the F-ALT design resulted in a higher success rate in resuming oral feeding compared with the C-ALT design (90.5% vs 54.6%, P = 0.032). CONCLUSIONS: Patients with head and neck cancer with T&T defects were associated with higher rates of secondary flap revision and a trend of delayed oral feeding. In the long term, improved oral feeding outcome with the F-ALT design was observed compared with the C-ALT design in the specific group with T&T defect.

Prognostic significance of positive surgical margins for scalp angiosarcoma.

BACKGROUND: Scalp angiosarcomas (AS) are aggressive soft tissue sarcomas that present with outcomes different from other AS of the head and neck region. Due to the rarity of the disease, limited data on the clinical outcome of scalp AS are available. In particular, the prognostic significance of surgical margins remains controversial and the impact of margin status on survival has not been documented. METHODS: We retrospectively reviewed 41 scalp AS patients, including 30 patients with localized disease and 11 patients with initial distant metastasis, treated in our institution between 1997 and 2017. Survival was determined by Kaplan-Meier analysis. In the 30 patients without distant metastasis (localized disease), univariate and multivariate analysis using the Cox proportional hazards model were used to determine clinicopathologic characteristics associated with recurrence free survival (RFS), locoregional control (LRC), and overall survival (OS). RESULTS: Totally 41 patients diagnosed with scalp AS were identified, including 30 patients with localized disease and 11 patients with initial distant metastasis on diagnosis. Overall, the median follow-up period was 19.3 (range 0.3-128.5) months. The median survival time was 16.6 (range 0.3-144.3) months and the 5-year OS (95% Confidence Interval (CI)) rate was 22% (12%-42%). In the 30 patients with localized disease, univariate analysis showed that positive margins, either lateral-side or deep-side, were significant prognostic factors for RFS, LRC, and OS (p < 0.05). On multivariate analysis, positive margins emerged as adverse prognostic factors for RFS (Hazard Ratio (HR) 4.29, 95% CI, 1.71-10.75, p = 0.002), LRC (HR 6.35, 95% CI, 2.19-18.37, p = 0.001), and OS (HR 4.73, 95% CI, 1.71-13.07, p = 0.003). CONCLUSION: Scalp AS is associated with high local recurrence rates and poor survival outcomes. Positive surgical margins are adverse prognostic factors for survival.

The impacts of intra-arterial chemotherapy on head and neck microvascular reconstruction.

BACKGROUND: For locally advanced head and neck cancers, intra-arterial (IA) chemotherapy is utilized for locoregional control with favorable results. The study aimed to evaluate the surgical outcomes of microsurgical reconstruction in head and neck cancer patients with IA chemotherapy METHODS: This cohort study retrospectively reviewed patients who underwent head and neck microsurgical reconstruction from January 2014 to August 2018. Patients with prior history of chemotherapy were included and categorized into two groups according to history of IA chemotherapy (IA group)/intravenous chemotherapy (IV group). Flap survival was evaluated along with microsurgical revision rates and complications. Recipient vessel specimens were analyzed by histological examination. A 1:1 propensity score matched analysis was performed. RESULTS: The study cohort included 45 patients with IA chemotherapy and 201 patients with IV chemotherapy. After propensity score matching, the difference in total flap loss and microsurgical revision rates were nonsignificant between two groups. However, the IA group had significantly higher rates of arterial thrombosis (Odds ratio [OR] 4.98; 95%CI, 1.28-19.38; p = 0.021), wound-related complications (OR 3.30; 95%CI, 1.21-9.02; p = 0.02) and revision surgery within one month (OR 3.73; 95%CI, 1.10-12.64; p = 0.035). Based on histology, IA group vessels showed a higher intima/media ratio than the IV group (0.45 ± 0.06 versus 0.23 ± 0.03, p = 0.02) CONCLUSION: Despite treating local advanced head and neck cancers with good results, IA chemotherapy may cause subsequent deleterious effects on local tissue due to the high concentration of cytotoxic chemotherapeutic agents. Surgeons should be cautious in selection of recipient vessels when performing microvascular reconstruction.

Interleukin-6 from Adipose-Derived Stem Cells Promotes Tissue Repair by the Increase of Cell Proliferation and Hair Follicles in Ischemia/Reperfusion-Treated Skin Flaps.

The most common postoperative complication after reconstructive surgery is flap necrosis. Adipose-derived stem cells (ADSCs) and their secretomes are reported to mediate skin repair. This study was designed to investigate whether conditioned media from ADSCs (ADSC-CM) protects ischemia/reperfusion- (I/R-) induced injury in skin flaps by promoting cell proliferation and increasing the number of hair follicles. The mouse flap model of ischemia was ligating the long thoracic vessels for 3 h, followed by blood reperfusion. ADSC-CM was administered to the flaps, and their survival was observed on postoperative day 5. ADSC-CM treatment led to a significant increase in cell proliferation and the number of hair follicles. IL-6 levels in the lysate and CM from ADSCs were significantly higher than those from Hs68 fibroblasts. Furthermore, a strong decrease in cell proliferation and the number of hair follicles was observed after treatment with IL-6-neutralizing antibodies or si-IL-6-ADSC. In addition, ADSC transplantation increased flap repair, cell proliferation, and hair follicle number in I/R injury of IL-6-knockout mice. In conclusion, IL-6 secreted from ADSCs promotes the survival of I/R-induced flaps by increasing cell proliferation and the number of hair follicles. ADSCs represent a promising therapy for preventing skin flap necrosis following reconstructive and plastic surgery.

Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen.

Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory, and antioxidative effects, but its effects on wound healing are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by haematoxylin and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear factor kappa B signalling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines.

CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology.

To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy was observed, as evidenced by reduced capillary luminal area, increased capillary basement membrane thickness and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves. In diabetic nerves, there was also significant macrophage and T cell infiltration, and cluster of differentiation 40 (CD40) expression was increased. The molecular alterations observed were upregulation of hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase-activated protein kinase 2 (MK2; MAPKAPK2) and phosphatase and tensin homolog (PTEN). In addition, HIF-1α was correlated with small myelinated fiber density and capillary luminal area, while both MK2 and PTEN were correlated with capillary basement membrane thickness. The molecular cascades were further demonstrated and replicated in a cell model of microangiopathy on human umbilical vein endothelial cells (HUVECs) exposed to high-glucose medium by silencing of CD40, PTEN and HIF-1α in HUVECs using shRNA. These data clarified the hierarchy of the molecular cascades, i.e. upregulation of CD40 leading to HIF-1α expression in endothelium and nerve fibers. In conclusion, this study revealed the association of microangiopathy, thrombosis and inflammatory infiltrates with nerve degeneration in diabetic nerves, demonstrating that CD40 is a key molecule for the upregulation of HIF-1α and PTEN underlying the severity of microangiopathy.

Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection.

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection.

Treatment and long-term follow-up of oral cancer postoperative sialorrhea with dermal sling operation.

INTRODUCTION: Reconstruction of a full-thickness defect that includes oral commissure presents a considerable challenge to maxillofacial and plastic surgeons. The goals of reconstruction are both functional and cosmetic. Sialorrhea, or drooling, is a major problem after flap reconstruction and influences the quality of life of the patient. In this article, we report on our experience performing a dermal sling operation to treat postoperative sialorrhea in patients with oral cancer. MATERIALS AND METHODS: Preoperative and postoperative levels of sialorrhea were evaluated based on the Drooling Severity and Frequency Scale. Dermal sling operations were performed on 27 patients from January 2000 to December 2013. In these patients, 12 cases were reviewed and followed up over 1 year. RESULTS: Of the 12 patients, 11 were men and one was a woman, with the mean age of 58 years (range, 40-79 years). There were no operative complications. The mean preoperative score was 4.75 (range, 3-7), and the mean postoperative score was 3.83 (range, 2-5). This change was significant (P=0.005), with valuation with the Wilcoxon signed rank test. The mean time of follow-up was 3.5 years (range, 1.1-7.7 years). CONCLUSIONS: The dermal sling operation is an acceptable treatment for postoperative sialorrhea in patients with commissure-involved oral cancer.

Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac bone flap to fibula flap in postoperative infection and healing.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is not an uncommon complication after radiotherapy for head and neck cancers. Although definitive treatment has been confirmed as radical excision of the necrotic bone with simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique challenge. In this study, we compare our results of reconstruction with free iliac and fibula flaps in flap survival, bony union, and postoperative complications. PATIENTS AND METHODS: From 1986 to 2011, there were 153 mandibular ORN cases in our center that were treated with radical resection of the necrotic bone and reconstruction with either vascularized iliac (n=108) or fibula flaps (n=45). Data collected for analysis included patient demographics, flap survival rate, postoperative infection rate, nonunion/malunion rate, mean hospital stay, and antibiotics use. RESULTS: All patients healed eventually without recurrence of ORN. However, we observed difference in the complication rate between the iliac flap group and fibula flap group. In the group with iliac flap reconstruction, patients required less days of hospital stay for intravenous antibiotics treatment postoperatively. The average days required for intravenous antibiotics in the iliac flap group were 10.46 (2.28) versus 16.09 (3.88) days in the fibula group (P<0.01). In the group with fibula flap reconstruction, 9 (20.0%) patients had subsequent neck infection due to healing problem, compared to 8 (7.4%) patients in the iliac flap group (P=0.04). In the iliac flap group, the nonunion and malunion rates were 4.6% and 2.8% respectively; whereas in the fibula group, the rates were 15.5% and 6.6%, respectively (P=0.04 and 0.36, respectively). CONCLUSIONS: For ORN patients, vascularized iliac bone flap provides more reliable results compared to fibula flap. The merits of vascularized iliac flap include the following: (1) its natural curve mimics the shape of mandible and does not need osteotomy; (2) it offers more volume of bone that matches better to the native mandible to allow later osteointegration as well as faster bony union, due to the nature of being a membranous bone; and (3) it carries more abundant soft tissue to obliterate possible dead space. The only disadvantages are short pedicle and requiring special management of skin paddle, which can be overcome by training in microsurgery.

A modified free chimeric osteocutaneous fibular flap design for head and neck reconstruction: experience on a series of 10 cases.

BACKGROUND: We have previously described a modified chimeric fibular osteocutaneous flap design based on a combination of a traditional fibular flap and a peroneal artery perforator fasciocutaneous flap for mandible and adjacent soft tissue reconstruction. The purpose of this article is to share our experience with a larger case series utilizing this new technique for mandible and adjacent soft tissue reconstruction after cancer wide excision surgery and a more detailed description on these flaps harvesting procedures. PATIENTS AND METHODS: Ten patients (age range from 32 to 63 years), who had segmental defect of mandible and adjacent soft tissue defect after cancer wide excision surgery, received mandible and adjacent soft tissue reconstruction based on the modified chimeric fibular flap design. RESULTS: The skin paddle based on peroneal perforators ranged from 9 cm × 3.5 cm to 10 cm × 10 cm and the mean pedicle length was 8.9 cm. Four patients underwent primary closure of the donor site. Three flap salvage procedures were performed due to vascular thrombosis and all flaps survived well. Nine patients had acceptable outer appearance, and one patient complained of cheek sunken. All patients had at least 3-cm interincisor distance during a mean of 12-month follow-up period. CONCLUSION: The modified chimeric osteocutaneous fibula flaps were feasible design with few intermuscular septum problems during bone fixation. Furthermore, it provided larger skin paddles with few restrictions to reconstruct the cheek skin defect.

Patterns of target tissue reinnervation and trophic factor expression after nerve grafting.

BACKGROUND: Reinnervation of target tissues determines functional outcomes after nerve grafting, which is important in traumatic injury caused by accidents or consequences resulting from surgical removal of tumors. Previous studies documented the influences of nerve repair mainly based on nerve morphometry but rarely compared the final outcomes according to target reinnervation patterns by nerve fibers of different categories. METHODS: In a mouse model of nerve grafting, the authors analyzed the innervation indexes of different target tissues after transection-reimplantation on the sciatic nerve, which were defined as a parameter on the operated side normalized to that on the control side. RESULTS: Muscle reinnervation appeared to be the best compared with skin reinnervation (p < 0.0001) and sweat gland reinnervation (p < 0.0001) at postoperative month 3. The sudomotor reinnervation was relatively higher than the cutaneous reinnervation (p = 0.014). The abundance of trophin transcripts for brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin 3 (NT3) was higher in plantar muscles on the operated side than those on the control side. In contrast, transcripts of BDNF, GDNF, nerve growth factor, and NT3 were all similar in the footpad skin between the operated and control sides. CONCLUSIONS: The results suggested that, compared with the skin, muscles achieved the best reinnervation after nerve grafting, which was related to higher expression of BDNF, GDNF, and NT3 in muscles than in the skin.

New modified free chimeric fibular flap design for head and neck reconstruction.

BACKGROUND: The free fibular osteocutaneous flap is a commonly used flap for mandible and buccal mucosa reconstruction in head and neck cancer surgery. However, the skin paddle restriction from the intermuscular septum often limits the soft tissue reconstruction. METHODS: We have proposed a new modified chimeric fibular osteocutaneous flap design based on the combination of a traditional fibular flap and a peroneal artery perforator fasciocutaneous flap to overcome the restriction from intermuscular septum. RESULTS: We successfully applied this modified chimeric free fibular osteocutaneous flap design to 2 patients after buccal cancer wide excision surgery. CONCLUSION: The modified free chimeric fibular flap can be easily applied to a segmental defect over the mandible and adjacent soft tissue without restrictions between the bone and the skin paddle. Furthermore, this skin paddle design can also serve as an extra skin paddle to reconstruct an outer cheek skin defect.

Patterns of nerve injury and neuropathic pain in ischemic neuropathy after ligation-reperfusion of femoral artery in mice.

Ischemia is an important etiology of painful neuropathies. We generated a mouse system of ischemic neuropathy by ligation-reperfusion of the femoral artery to mimic neuropathic pain and nerve injury patterns observed clinically. Mice exhibited spontaneous neuropathic pain behaviors, which were most obvious after ischemia for 5 h. Mechanical and cold allodynia developed by post-operative day (POD) 7 and persisted through the experimental period up to POD 56. Neuropathic pain behaviors were alleviated with intraperitoneal gabapentin (50 and 100 mg/kg) in a dose-dependent manner. Large-fiber deficit assessed with nerve conduction studies was demonstrated by reduced amplitudes of the compound muscle action potential (CMAP) on POD 7 (48.4% of the control side, p < 0.001). Small-fiber impairment was demonstrated by decreased epidermal nerve density (END) on POD 7 (29.1% of the control side, p < 0.001). Reductions in CMAP amplitudes and ENDs persisted through POD 56. Our system replicated the clinical manifestations of ischemic neuropathy: (1) neuropathic pain with cold and mechanical allodynia and (2) nerve injury to both large and small fibers with pathologic and physiologic evidence. This system produced by a simple procedure provides an opportunity to investigate mechanisms and further treatments of ischemic neuropathy on genetically engineered mice.

Cutaneous infection caused by Gordonia amicalis after a traumatic injury.

Gordonia amicalis infection has never been reported in humans. We report here the first case of G. amicalis-related cutaneous infection after a traumatic injury. The isolate was confirmed by 16S rRNA sequencing analysis, and the patient responded well to repeated debridement and antibiotic treatment.