Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

Intraoperative Real-Time Visualization of the Lymphatic Vessels Using Microscope-Integrated Laser Tomography.

BACKGROUND: Detection and selection of the lymphatic vessels are important for maximizing therapeutic efficacy of lymphaticovenular anastomosis (LVA). Some imaging modalities have been reported to be useful for intraoperative identification of the lymphatic vessels, but they have limitations. In this article, we present new capabilities of intraoperative laser tomography, which was used to evaluate the lumen of the lymphatic vessel and to validate the patency of anastomosis. METHODS: Fifty-two patients with upper extremity lymphedema secondary to breast cancer treatment underwent indocyanine green (ICG) lymphography and real-time laser tomography imaging of ICG-enhanced lymphatic vessels intraoperatively before transecting the vessels during LVA. The imaging findings of the lymphatic vessels in laser tomography were investigated. Time required for scanning of the lymphatic vessels was compared between laser tomography and ultrasonography. The correlation between the thickness of the lymphatic vessel wall measured with laser tomographic imaging and the histologically measured thickness of the lymphatic vessel wall was examined. The patency of anastomosis sites was determined based on the image using laser tomography immediately after establishment of LVA. RESULTS: A total of 132 ICG-enhanced lymphatic vessels were scanned with laser tomography showing clear lumen with surrounding vessel wall. The required time for lymphatic vessel scanning was significantly shorter with laser tomography than with ultrasonography (1.6 ± 0.3 vs. 4.8 ± 1.2 minutes; p = 0.016). Strong correlation was seen between the thickness of the lymphatic vessels wall measured using laser tomography and the histologically measured thickness of the lymphatic vessel wall (r = 0.977, 95% confidence interval: 0.897-0.992, p < 0.001). The quality of patency was evaluated immediately after anastomosis, which assisted in deciding whether reanastomosis was needed. CONCLUSION: Microscope-integrated laser tomography provides real-time images of the lymphatic vessels in extremely high resolution and enables evaluation of lymphatic lumen condition and objective post-LVA anastomosis status.

Comparison of the outcomes between free anteromedial thigh flap and anterolateral thigh flap in head and neck cancer reconstruction: Analysis of propensity-score-matched patient cohorts.

BACKGROUND: The anterolateral thigh (ALT) flap is a workhorse flap in head and neck cancer reconstruction. The anteromedial thigh (AMT) flap was developed as a rescue or alternative flap whenever the ALT flap is not available; however, the harvest of AMT flap seems to be more challenging in the sense that perforators have multiple variations. This study was designed to compare the outcome of the AMT and ALT flaps in head and neck cancer reconstruction. METHODS: A total of 1,547 ALT and 57 AMT flaps were used for head and neck cancer reconstruction between March 1, 2008 and February 28, 2017. Differences in patient and operative characteristics were compared between the patients undergoing AMT and ALT flap reconstruction. The primary outcome of the free flap was its survival or failure, while the second outcome was the associated complications. RESULTS: Compared to those who had ALT flap reconstruction, the patients who underwent AMT flap reconstruction had a higher rate of conditions that required reconstruction after previous cancer ablation and recurrence but a lower rate of primary cancer and deeply located cancer. Analysis of the 40 well-balanced pairs of propensity-score-matched patient cohorts revealed that the AMT flaps were associated with a significantly higher failure rate than the ALT flaps (15.0 vs. 0.0%, respectively; p = .026). CONCLUSION: This study revealed that AMT flaps were associated with a significantly higher failure rate than ALT flaps in head and neck cancer reconstruction in the cohort of total patients and the propensity-score-matched cohorts.

Microsurgical head and neck reconstruction in patients with coronary artery disease: A perioperative assessment algorithm.

BACKGROUND: With the rising number of patients in advanced age receiving microsurgical procedures, coronary artery disease (CAD) and its challenging management is of increasing importance. Evidence based data concerning morbidity and mortality are rare. We present our experiences with this highly selected patient population and propose a preoperative assessment algorithm. PATIENTS AND METHODS: Between January 2006 and May 2016, a total of 57 patients with CAD received 58 free flaps. Median age of our patients was 64 years (interquartile range 57.5-70.0). Squamous cell carcinoma was the reason for reconstruction in all cases. Defect of the buccal, gum, tongue, lip, trigone, palatal, and hypopharyngeal regions were reconstructed. Patient characteristics and comorbidities were recorded. We especially focused on the preoperative cardiac assessment and treatment of patients who were scheduled for microsurgical free tissue transfer such as medical history, cardiac risk assessment, and further cardiac testing such as Doppler-echocardiography and myocardial perfusion assessment. Intraoperative course as well as postoperative morbidity and mortality was described. RESULTS: About 54.4% of the selected cohort received cardiac catheterization due to a clinical preoperative cardiac assessment performed individually by the cardiologist on duty. In total, 52 fasciocutaneous anterolateral thigh flaps, four osteocutaneous fibula flaps, and two radial forearm flaps were performed. The flap survival rate was 96.6%. The overall surgical complication rate was 28.1% (16 patients), mostly due to wound infections (seven cases) and partial flap necrosis (four cases). Three patients died, resulting in a mortality rate of 5.2%. CONCLUSION: CAD patients receiving head and neck microsurgical reconstructions are still at high risk for adverse consequences due to surgery. The microsurgical community is requested to share the experience of those cases in order to develop reliable and evidence based statements of the perioperative risks and prognosis for these patients. We additionally introduce a standardized perioperative cardiac assessment and treatment algorithm for head and neck surgery patients with CAD.

Intraoperative identification and definition of "functional" lymphatic collecting vessels for supermicrosurgical lymphatico-venous anastomosis in treating lymphedema patients.

BACKGROUND: For current lymphatico-venous anastomosis (LVA), the identification of "functional" lymphatic collecting vessels (LCVs) is mainly based on indocyanine green (ICG) lymphography. However, some of the non-ICG enhanced LCVs utilized for LVA were found to have visual lymphatic flow. OBJECTIVES: Should non-ICG enhanced, but flow-positive LCVs be considered functional as well? METHODS: A retrospective study with 56 consecutive lymphedema patients (8 male/48 female) received LVA. LCVs were observed after ICG injection, before/after LVAs were performed. ICG enhancement and lymphatic flow in the LCVs were recorded and grouped as: Group A: all LCVs ICG(+) and flow(+); Group B: all LCVs ICG(+) and some were flow(+); Group C: some ICG(+) and some flow(+) LCVs; Group D: all LCVs ICG(-)but all flow(+); and Group E: all LCVs were both ICG(-) and flow(-). RESULTS: A total of 366 LCVs were identified, averaging 8.2 LVAs, 6.5 LCVs, and 4.7 veins per patient. A total of 33 LVAs were performed with 27 LCVs with no ICG enhancement from 7 patients (Group D). These patients were satisfied with their lymphedema improvements. CONCLUSION: Lymphatic flow-positive but non-ICG enhanced LCVs, should also be considered as functional, thereby maximizing the number of functional LCVs for LVA.

The free inverted omega-shaped flap for circumferential hypopharyngeal reconstruction with simultaneous neck skin defect.

BACKGROUND: Circumferential hypopharyngeal defect with simultaneous skin defect can pose complicated reconstructive challenge for reconstructive microsurgeons. Our experience with the versatile inverted-omega flap tubing design is proposed to accommodate such problem. METHODS: From 2012 to 2015, 13 anterolateral thigh (ALT) flaps and one anteromedial thigh (AMT) flap were harvested for reconstruction of circumferential hypopharyngeal defects with skin defects in 14 patients. All patients were males except one. Patient age ranged from 42 to 67 years (average, 53.1 years). Fifty-seven percent were recurrent cases. All but one patient received preoperative chemoradiotherapy. RESULTS: The average flap size was 29 × 8 cm (range: 25-31 × 6-10 cm2 ). An average of 2.6 perforators was included in each flap (2-4 perforators/flap). All flaps survived. One venous thrombosis was noted and salvaged after thrombolectomy and vein graft. The mean follow-up period was 25 months. The fistula rate was 21.4% (three patients). One fistula never healed because of early recurrence; one fistula healed after surgical intervention; and one fistula need a loco-regional flap for secondary reconstruction. Three postoperative strictures were noted (21.4%). CONCLUSION: For the circumferential hypopharyngeal defect with simultaneous neck skin defect, this inverted-omega ALT tubing design offers an alternative choice for such complicated reconstruction. © 2016 Wiley Periodicals, Inc. Microsurgery, 38:51-59, 2018.

Weight-reduction through a low-fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice.

BACKGROUND: To examine the circulating microRNA (miRNA) expression profile in a mouse model of diet-induced obesity (DIO) with subsequent weight reduction achieved via low-fat diet (LFD) feeding. RESULTS: Eighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal %) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal % high-fat diet (HFD) for 12 weeks; and (3) DIO + LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal % LFD for 4 weeks. A switch to LFD feeding led to decreases in body weight, adiposity, and blood glucose levels in DIO mice. Microarray analysis of miRNA using The Mouse & Rat miRNA OneArray® v4 system revealed significant alterations in the expression of miRNAs in DIO and DIO + LFD mice. Notably, 23 circulating miRNAs (mmu-miR-16, mmu-let-7i, mmu-miR-26a, mmu-miR-17, mmu-miR-107, mmu-miR-195, mmu-miR-20a, mmu-miR-25, mmu-miR-15b, mmu-miR-15a, mmu-let-7b, mmu-let-7a, mmu-let-7c, mmu-miR-103, mmu-let-7f, mmu-miR-106a, mmu-miR-106b, mmu-miR-93, mmu-miR-23b, mmu-miR-21, mmu-miR-30b, mmu-miR-221, and mmu-miR-19b) were significantly downregulated in DIO mice but upregulated in DIO + LFD mice. Target prediction and function annotation of associated genes revealed that these genes were predominantly involved in metabolic, insulin signaling, and adipocytokine signaling pathways that directly link the pathophysiological changes associated with obesity and weight reduction. CONCLUSIONS: These results imply that obesity-related reductions in the expression of circulating miRNAs could be reversed through changes in metabolism associated with weight reduction achieved through LFD feeding.

Altered exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury.

BACKGROUND: The NF-κB signaling pathway plays a role in local and remote tissue damage following ischemia-reperfusion (I/R) injury to skeletal muscles. Evidence suggests that exosomes can act as intercellular communicators by transporting active proteins to remote cells and may play a role in regulating inflammatory processes. This study aimed to profile the exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury. RESULTS: To investigate the potential changes in protein expression mediated by NF-κB in secreted exosomes in the serum following I/R injury, the levels of circulating exosomal proteomes in C57BL/6 and NF-κB(-/-) mice were compared using two dimensional differential in-gel electrophoresis (2-DE), liquid chromatography tandem mass spectrometry (LC-MS/MS), and proteomic analysis. In C57BL/6 mice, the levels of circulating exosomal proteins, including complement component C3 prepropeptide, PK-120 precursor, alpha-amylase one precursor, beta-enolase isoform 1, and adenylosuccinate synthetase isozyme 1, increased following I/R injury. However, in the NF-κB(-/-) mice, the expression of the following was upregulated in the exosomes: protease, serine 1; glyceraldehyde-3-phosphate dehydrogenase-like isoform 1; glyceraldehyde-3-phosphate dehydrogenase; and pregnancy zone protein. In contrast, the expression of apolipoprotein B, complement component C3 prepropeptide, and immunoglobulin kappa light chain variable region was downregulated in NF-κB(-/-) mice. Bioinformatic annotation using the Protein Analysis Through Evolutionary Relationships (PANTHER) database revealed that the expression of the exosomal proteins that participate in metabolic processes and in biological regulation was lower in NF-κB(-/-) mice than in C57BL/6 mice, whereas the expression of proteins that participate in the response to stimuli, in cellular processes, and in the immune system was higher. CONCLUSIONS: The data presented in this study suggest that NF-κB might regulate exosomal protein expression at a remote site via circulation following I/R injury.

Profiling the circulating miRNAs in mice exposed to gram-positive and gram-negative bacteria by Illumina small RNA deep sequencing.

BACKGROUND: We profiled the expression of circulating microRNAs (miRNAs) in mice using Illumina small RNA deep sequencing in order to identify the miRNAs that may potentially be used as biomarkers to distinguish between gram-negative and gram-positive bacterial infections. RESULTS: Recombinant-specific gram-negative pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus aureus (Xen29) were used to induce bacterial infection in mice at a concentration of 1 × 10(8) bacteria/100 µL of phosphate buffered saline (PBS). Small RNA libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29, and Xen14 + Xen29 via the routes of subcutaneous injection (I), cut wound (C), or under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer. Following exposure to gram-negative bacteria alone, no differentially expressed miRNA was found in the injection, cut, or skin graft models. Exposure to mixed bacteria induced a similar expression pattern of the circulating miRNAs to that induced by gram-positive bacterial infection. Upon gram-positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. Among them, mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p presented the most common miRNA targets expressed in the mice exposed to gram-positive bacterial infection. CONCLUSIONS: This study identified mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p as potential circulating miRNAs for gram-positive bacterial infections.

Posteromedial thigh (PMT) propeller flap for perineoscrotal reconstruction: A case report.

Fournier's gangrene can lead to extensive defects of the perineoscrotal area with exposure of the testes. Such defect poses challenging tasks for both functional and cosmetic reconstruction. Due to its proximity, medial thigh skin appeared to be the most versatile donor site for perineoscrotal reconstruction. In this report, we present a case of reconstruction of a large perineoscrotal defect because of Fournier's gangrene using a posteromedial thigh (PMT) perforator propeller flap. A 58 year-old male who suffered from Fournier's gangrene resulted in a scrotal defect of 10 × 12 cm(2) with a large dead space. A pedicled PMT propeller flap measuring 9 × 23 cm(2) with two perforators that originated from the profunda femoris artery (PFA) was harvested for scrotal defect reconstruction and dead space obliteration. The flap survived completely, with no recipient or donor site morbidity. The length of followup was 3 months and was uneventful. The pedicled PMT propeller flap may be considered as a valid option for perineoscrotal reconstruction.

Inhibition of the phosphoinositide 3-kinase pathway decreases innate resistance to lipopolysaccharide toxicity in TLR4 deficient mice.

BACKGROUND: Upon lipopolysaccharide (LPS) stimulation, activation of both the Toll-like receptor 4 (TLR4) and phosphoinositide 3-kinase (PI3K) pathways serves to balance proinflammatory and anti-inflammatory responses. Although the antagonist to TLR4 represents an emerging promising target for the treatment of sepsis; however, the role of the PI3K pathway under TLR4-null conditions is not well understood. This goal of this study was to investigate the effect of inhibition of PI3K on innate resistance to LPS toxicity in a murine model. RESULTS: The overall survival of the cohorts receiving intraperitoneal injections of 100, 500, or 1000 µg LPS from Escherichia coli serotype 026:B6 after 7 d was 100%, 10%, and 10%, respectively. In contrast, no mortality was noted after 500-µg LPS injection in Tlr4-/- mice. When the PI3K inhibitor LY294002 was injected (1 mg/25 g body weight) 1 h prior to the administration of LPS, the overall survival of the Tlr4-/- mice was 30%. In the Tlr4-/- mice, the LPS injection induced no NF-κB activation but an increased Akt phosphorylation in the lung and liver, when compared to that of the C57BL/6 mice. Injection of 500 µg LPS led to a significant induction in O2⁻ detected by electron paramagnetic resonance (EPR) spin trapping spectroscopy in the lung and liver at 3 and 6 h in C57BL/6 but not Tlr4-/- mice. Addition of LY294002 only significantly increased the O2⁻ level in the lung and liver of the Tlr4-/- mice but not in the C57BL/6 mice following 500-µg LPS injection. In addition, the serum IL-1ß and IL-2 levels were more elevated in C57BL/6 mice than in Tlr4-/- mice. Notably, IL-1ß and IL-2 were significantly increased in Tlr4-/- mice but not in the C57BL/6 mice when the PI3K pathway was inhibited by LY294002 prior to LPS injection. CONCLUSIONS: In this study, we demonstrate that innate resistance to LPS toxicity in Tlr4-/- mice is impaired by inhibition of the PI3K pathway, with a corresponding increase in mortality and production of tissue O2⁻ and inflammatory cytokines.

Secondary subdermal pocket procedure for venous insufficiency after digital replantation/revascularization.

PURPOSE: Venous insufficiency after microsurgical replantation/revascularization remained to be a vexing problem for finger failure, despite the level of amputation. Other than redo the venous anastomosis, alternative methods such as subdermal pocket procedure (SDP) can be used. The aim of this study was to incorporate SDP immediately at the time of replantation, when no suitable vein is available after digital artery anastomosis; or, as a secondary salvage procedure to restore venous drainage for venous insufficiency after initial digital replantation/revascularization. MATERIALS AND METHODS: From 1999 to 2010, a total of 21 injured digits from 20 patients were collected. The mechanisms of injury included 6 guillotine amputations, 1 guillotine near-complete amputation, 12 crushing amputations, 1 crushing injury, and 1 crushing injury with contact thermal burn. The average patients' age was 34.5 years. Subdermal pocket procedures were used to all injured digits at different time frame as indicated. The patients were divided into 2 groups based on the timing of SDP, either primary or secondary. The pocketing period and the time lapse between the initial operation and the secondary salvaged SDP were also documented. RESULTS: Group 1 (13 digits) received primary SDP as means of venous drainage immediately after digital artery revascularization. The mean pocketing period was 9.2 days, ranging from 7 to 15 days, with a 100% complete survival rate. Group 2 (8 digits) received secondary SDP as a salvage procedure when venous congestion became apparent later. The mean time lapse between initial operation and salvaged SDP was 53.1 hours. The average pocketing period was 7.5 days, with a 75% survival rate. CONCLUSIONS: Secondary SDP provides an alternative salvage solution for postreplantation venous insufficiency without the need for further microsurgery.

The role of the anterolateral thigh flap in complex defects of the scalp and cranium.

In this study, we introduced scalp reconstruction using free anterolateral thigh (ALT) flaps and evaluated postoperative outcomes in nine patients between March 2000 and April 2012. Five patients had problems of exposed prosthesis, three required reconstruction after resection of scalp tumor and one patient presented with third degree flame burns of the scalp. All flaps survived without re-exploration, except three flaps with tip necrosis requiring secondary procedures of debridement and small Z-plasty reconstructions. The superficial temporal artery and its concomitant vein were used as recipient vessels, apart from two cases where previous surgery and flame burns excluded these choices, for which facial arteries and veins were used instead. Primary closure of the donor-site was possible in six cases; with skin grafting performed for the other three patients. All donor sites healed without complications. The ALT flap offers the advantage of customizable size, option of fascia lata as vascularized dural replacement, and minimal flap atrophy typical of muscle flaps. Indications include very large defects, defects with exposed prosthesis, or defects with bone or dural loss. Our experience lends credible support to the use of customized free ALT flaps to achieve functional and cosmetically superior result for the reconstruction of large scalp defects, especially with bone exposure.

Comparison of contraction-type and noncontraction-type lymphatic vessels in lymphaticovenous anastomosis for cancer-related unilateral lower limb lymphedema: a retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.

Circulating microRNA signatures in mice exposed to lipoteichoic acid.

BACKGROUND: Previously, we had identified a specific whole blood-derived microRNAs (miRNAs) signature in mice following in vivo injection of lipopolysaccharide (LPS) originated from Gram-negative bacteria. This study was designed to profile the circulating miRNAs expression in mice exposed to lipoteichoic acid (LTA) which is a major component of the wall of Gram-positive bacteria. RESULTS: C57BL/6 mice received intraperitoneal injections of 100 µg of LTA originated from Bacillus subtilis, Streptococcus faecalis, and Staphylococcus aureus were killed 6 h and the whole blood samples were obtained for miRNA expression analysis using a miRNA array (Phalanx miRNA OneArray® 1.0). Up-regulated expression of miRNA targets in the whole blood, serum and white blood cells (WBCs) of C57BL/6 and Tlr2-/- mice upon LTA treatment in 10, 100, or 1000 ug concentrations was quantified at indicated time (2, 6, 24, and 72 h) using real-time RT-PCR and compared with that in the serum of C57BL/6 mice injected with 100 ug of LPS. A significant increase of 4 miRNAs (miR-451, miR-668, miR-1902, and miR-1904) was observed in the whole blood and the serum in a dose- and time-dependent fashion following LTA injection. Induction of miRNA occurred in the serum after 2 h and persisted for at least 6 h. No increased expression of these 4 miRNAs was found in the WBCs. Higher but not significant expression level of these 4 miRNAs were observed following LTA treatment in the serum of Tlr2-/-against that of C57BL6 mice. In contrast, LPS exposure induced moderate expression of miR-451 but not of the other 3 miRNA targets. CONCLUSIONS: We identified a specific circulating miRNA signature in mice exposed to LTA. That expression profile is different from those of mice exposed to LPS. Those circulating miRNAs induced by LTA or LPS treatment may serve as promising biomarkers for the differentiation between exposures to Gram-positive or Gram-negative bacteria.

Profiling circulating microRNA expression in a mouse model of nerve allotransplantation.

BACKGROUND: The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression. RESULTS: Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative real-time PCR (qRT-PCR). Three circulating miRNAs (miR-320, miR-762, and miR-423-5p) were identified in the whole blood and serum of the mice receiving an allograft with FK506 immunosuppression, within 2 weeks after nerve allotransplantation. However, these 3 circulating miRNAs were not expressed in the nerve grafts. The expression of all these 3 upregulated circulating miRNAs significantly decreased at 2, 4, and 6 d after discontinuation of FK506 immunosuppression. In the nerve graft, miR-125-3b and miR-672 were significantly upregulated in the mice that received an allograft with FK506 only at 7 d after nerve allotransplantation. CONCLUSIONS: We identified the circulating miR-320, miR-762, and miR-423-5p as potential biomarkers for monitoring the immunosuppression status of the nerve allograft. However, further research is required to investigate the mechanism behind the dysregulation of these markers and to evaluate their prognostic value in nerve allotransplantation.

Use of anteromedial thigh flaps as an alternative to anterolateral thigh flaps for reconstruction of head and neck defects in cancer patients.

BACKGROUND: To determine whether anteromedial thigh (AMT) flaps are a good choice for reconstruction in cases in which no sizable skin perforator is found in anterolateral thigh (ALT) flap dissection or ALT flaps have been previously harvested. METHODS: From February 2006 to August 2008, 17 free AMT flaps were used to reconstruct soft tissue defects of the head and neck. We recorded the age and sex of the patients, sites of primary tumor, tumor stage, size of defect, previous operative conditions, results of flap transfer, and donor-site complications. RESULTS: Of the 17 AMT flaps, 1 flap failed and 1 showed partial necrosis. Venous insufficiency developed in 2 cases, and the flaps were successfully salvaged in both the cases. The success rate was 94.1%. The AMT flaps were 6 to 20 cm long and 4 to 9 cm wide. The mean length of the pedicle was 7.5 ± 1.0 cm (range, 5-12 cm). Of the 17 donor sites, 6 were closed directly, 9 were closed using split-thickness skin grafts, and 2 were closed using full-thickness skin grafts. Complications and morbidity of the donor site were minimal. CONCLUSIONS: Cases in which no sizable perforator is found or an ALT flap has been previously harvested pose an aesthetic challenge, and an AMT flap is a good alternative for performing successful reconstruction in such cases.

Lymphatic-based Lymphosome: A Novel Hypothesis with Clinical Implication for Supermicrosurgical Lymphaticovenous Anastomosis.

Understanding the anatomical territories drained by lymphatic vessels (LVs) is essential for a better comprehension of lymphatic anatomy and functionality, and for performing lymphatic procedures such as lymphaticovenous anastomosis (LVA). However, current concepts regarding the lymphatic territory are insufficient to explain some of the clinical observations. As shown in the figures, within one incision for the LVA, one to two lymphatic vessels (LV) remained unenhanced on indocyanine green (ICG) lymphography, whereas the rest of the LVs were enhanced. To answer this question, one must examine the concept of the lymphosome, first described by Suami, defined as a particular region drained by LVs into the same subgroup of regional lymph nodes (LNs) (eg, superficial groin LNs). Suami's lymphosome concept represents "LN-based lymphosomes." In addition, Shinaoka identified four distinct lymphatic groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limbs after ICG injection. This represents the concept "group-based lymphosomes." Nevertheless, neither the LN- nor group-based lymphosome concepts offer an appropriate explanation for the clinical findings described above. In addition to the aforementioned lymphosome concepts, the author proposes a novel hypothesis called "lymphatic-based lymphosome," which considers each LV as a single lymphosome. Therefore, the normal-type LV remained unenhanced when ICG was not injected into the draining territory. To enhance post-LVA outcomes, an even distribution of anastomoses to different group-based lymphosomes is important, as is avoiding performing all anastomoses onto a single LV or within the same group-based lymphosome.

Density Spectral Array Enables Precise Sedation Control for Supermicrosurgical Lymphaticovenous Anastomosis: A Retrospective Observational Cohort Study.

Supermicrosurgical lymphaticovenous anastomosis (LVA) is a minimally invasive surgical technique that creates bypasses between lymphatic vessels and veins, thereby improving lymphatic drainage and reducing lymphedema. This retrospective single-center study included 137 patients who underwent non-intubated LVA in southern Taiwan. A total of 119 patients were enrolled and assigned to two study groups: the geriatric (age ≥ 75 years, n = 23) and non-geriatric groups (age < 75 years, n = 96). The primary outcome was to investigate and compare the arousal and maintenance of the propofol effect-site concentration (Ce) using an electroencephalographic density spectral array (EEG DSA) in both groups. The results showed that the geriatric group required less propofol (4.05 [3.73-4.77] mg/kg/h vs. 5.01 [4.34-5.92] mg/kg/h, p = 0.001) and alfentanil (4.67 [2.53-5.82] µg/kg/h vs. 6.68 [3.85-8.77] µg/kg/h, p = 0.047). The median arousal Ce of propofol among the geriatric group (0.6 [0.5-0.7] µg/mL) was significantly lower than that in patients aged ≤ 54 years (1.3 [1.2-1.4] µg/mL, p < 0.001), 55-64 years (0.9 [0.8-1.0] µg/mL, p < 0.001), and <75 years (0.9 [0.8-1.2] µg/mL, p < 0.001). In summary, the combined use of EEG DSA provides the objective and depth of adequate sedation for extensive non-intubated anesthesia in late-elderly patients who undergo LVA without perioperative complications.