Bacterial Colonization on Endoscopic Materials and Surgical Field Without Infections After Transoral Endoscopic Thyroidectomy.

INTRODUCTION: Our aim was to determine whether bacteria contamination occurred within the surgical field or on endoscopic equipment during surgery using the transoral endoscopic thyroidectomy vestibular approach (TOETVA). MATERIALS AND METHODS: Participants were recruited from patients planned for TOETVA between May 2017 and December 2019. Bacterial samples were taken before and at the conclusion of the TOETVA procedure. The preoperative and postoperative samples were taken from the endoscopic materials and inferior oral vestibulum using a sterile flocked swab. RESULTS: The study resulted in 480 samples (80 TOETVAs). No vestibular, port site, or neck infections occurred in any of the patients. Three (3.7%) out of 80 patients developed postoperative fever. Our results show different microbial communities during TOETVA. The most prevalent species detected were Streptococcus species. Multivariate logistic regression analyses revealed that the degree of contamination depended on the sampling site (inferior vestibulum > equipment) (P=0.03). In addition, the abundance of bacteria was affected by operative time (P=0.013). There were no significant differences observed in isolation frequencies of bacteria in malignancy (P=0.34). CONCLUSIONS: TOETVA surgery is categorized as a "clean-contaminated" operation. A swab identified the common colonizers of oral microbiota on the endoscopic equipment and within the surgical field.

Enhanced mitigation of inhalable particles and fine particle-bound PAHs from a novel hazardous waste-power plant candidate.

Emissions of the inhalable particle (dp < 10 µm, PM10) and their harmful compositions from combustion sources have high potential on health risk with nearly no regulation. This study investigates the particle size distribution (PSD), as well as the removal mechanism of PM10 and fine particle (FP)-bound polycyclic aromatic hydrocarbons (PAHs) from the flue gas of a hazardous waste thermal treatment system. It has ultralow regulated emission and becomes a candidate of power generation module. A series of the advanced scrubbers, cyclonic demister, and baghouse was equipped for multi-pollutant control. The moderate or intense low oxygen dilution (MILD) combustion effectively inhibited the PM2.5 generation by volumetric oxidation. Advanced scrubbers removed PM1, PM2.5, and PM10 by 85.24, 68.68, and 97.60%, respectively, which achieved by local supersaturation, heterogeneous condensation of water vapor, and the growth of fine PM. Moreover, the scrubbers effectively scavenged the course PM10 containing the high-molecular-weight PAH homologs onto the water phase but promoted the condensation and absorption of the lighter homologs onto the fine particle surface (dp ∼5.3 µm). The size window (dp = 0.3-1.0 µm) of the minimum efficiency reporting value of a BH filtration led to the peak of FP-PAH mass and BaP equivalent (BaPeq) toxicity at dp = 0.1-0.4 and 0.1-0.8 µm, respectively. Consequently, the synergy of MILD combustion and the SCB-CYC-BH system effectively inhibited the PM2.5, PM10, PM2.5-PAHs, and FP-PAH levels from a waste thermal treatment process and further mitigated the potential health risk.

Bilayer osteochondral graft in rabbit xenogeneic transplantation model comprising sintered 3D-printed bioceramic and human adipose-derived stem cells laden biohydrogel.

Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D ß-tricalcium phosphate (ß-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D ß-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D ß-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D ß-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D ß-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D ß-TCP bioceramic scaffold.

Exosomes Derived from Hypoxia-Cultured Human Adipose Stem Cells Alleviate Articular Chondrocyte Inflammaging and Post-Traumatic Osteoarthritis Progression.

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O2 and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-ß-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy.

Relationships between serum levels of vitamins and papillary thyroid cancer: a single center case-control study.

Background: Vitamins are involved in various human physiological and biochemical mechanisms due to their antioxidant properties and their ability to enhance the immune response. Deficiency of some serum vitamins has been reported to be associated with an increased risk of developing cancer, including thyroid cancer. However, medical literature dealing with cholecalciferol supplementation was not able to show the potential of this intervention in cancer prevention. The aim of this paper is to highlight the association between lower serum vitamins levels and papillary thyroid cancer occurrence. Methods: This case-control study was conducted between September 2018 and October 2019. Cases were defined as patients with histologically diagnosed papillary thyroid cancer who underwent thyroidectomy were retrospectively recruited and serum levels of various vitamins were assessed by examining their relationships with clinical, pathological and molecular data (n=51). Controls matched on sex and thyroid surgery were randomly selected from the same population (n=49). Results: In this study, serum concentrations of vitamins A and E in neoplastic patients were significantly lower than in controls (1.40 vs. 1.78, P<0.003 and 23.9 vs. 29.1, P<0.003, respectively). Serum concentrations of vitamin D and methylmalonic acid were borderline significantly low (15.6 vs. 17.9, P=0.06 and 100.3 vs. 110.4, P=0.055, respectively), while homocysteine was statistically similar in the two groups. Furthermore, serum vitamin levels were compared with the pathological characteristics of cancer patients, and vitamin D concentrations were significantly lower in BRAF-positive than in BRAF-negative neoplastic patients (8.2 vs. 16.0, P=0.021). On the other hand, no significant differences were observed in the correlation between serum levels of vitamins and other pathological characteristics, in particular with regard to lymph node metastases. Conclusions: In conclusion, albeit with the analysis of a limited sample, this study highlighted the phenomenon that deficiencies in vitamins A and E can be associated with a higher frequency of occurrence of papillary thyroid cancer.

Growth Regulated Oncogene-α Upregulates TNF-α and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma.

Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Groα) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Groα-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Groα was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Groα, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Groα increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Groα, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Groα is the major stimulus of inflammatory mediation and promotes TNF-α (tumor necrosis factor-α) and COX-2 (cyclooxygenase-2) expression in HNSCC. Groα induces TNF-α and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)- and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Groα is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Groα and NOD1 in mediating metastasis and its potential as a therapeutic target.

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

3D Transoral Endoscopic Thyroid.

Transoral endoscopic thyroidectomy with vestibular approach (TOETVA) is a feasible new surgical procedure that does not require visible incisions. We describe our experience with three-dimensional (3D) TOETVA. We recruited 98 patients who were willing to undergo 3D TOETVA. Inclusion criteria were: (a) patients with a neck ultrasound (US) with an estimated thyroid diameter of 10cm or less; (b) estimated US gland volume ≤45ml; (c) nodule size ≤50mm; (d) benign tumor, such as thyroid cyst, goiter with one nodule, or goiter with multiple nodules; (e) follicular neoplasia; and (f) papillary microcarcinoma without evidence of metastases. The procedure is performed using a three-port technique at the oral vestibule, a 10mm port for the 30° endoscope, and two additional 5mm ports for dissecting and coagulation instruments. The CO2 insufflation pressure is set at 6mmHg. An anterior cervical subplatysmal space is created from the oral vestibule to the sternal notch and laterally to the sternocleidomastoid muscle. Thyroidectomy is performed entirely 3D endoscopically with conventional endoscopic instruments and intraoperative neuromonitoring. There were 34% total thyroidectomies and 66% hemithyroidectomies. Ninety-eight 3D TOETVA procedures were successfully performed without any conversions. The mean operative time was 87.6 minutes (59-118 minutes) for lobectomy and 107.6 minutes (99-135 minutes) for bilateral surgery. We observed one case of transient postoperative hypocalcemia. Paralysis of the recurrent laryngeal nerve did not occur. The cosmetic outcome was excellent in all patients. This is the first case series of 3D TOETVA.

Comparison of EMG amplitudes recorded by ipsilateral and contralateral electrodes placement during using trans-thyroid cartilage recording method in thyroid surgery.

Objectives: The feasibility and reliability of trans-thyroid cartilage EMG recording method (TCERM) during intraoperative monitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery have been established. This study compared two different recording electrode placements on the ipsi-lateral and contra-lateral lamina of the thyroid cartilage (TC). Methods: Fifty consecutive patients undergoing total thyroidectomy with 100 RLNs at risk were enrolled. Two paired subdermal needle electrodes were inserted into the subperichondrium of the bilateral TC lamina to record electromyography (EMG) signals. The channel leads from the TC electrodes were connected to the patient interface with two different modes. In A-mode, the electrode leads were placed ipsi-laterally, and channel 1 monitored the left RLN and channel 2 monitored the right RLN respectively. In B-mode, the electrode leads were placed contra-laterally, and channels 1 and 2 simultaneously monitored the same side of the RLN. The amplitudes of four EMG signals (V1-R1-R2-V2) recorded by A-mode and B-mode were compared. Results: All EMG amplitudes of V1-R1-R2-V2 signals recorded with B-mode were all above 500µV and significantly higher than those with A-mode (p<0.001). No false loss of signal, electrode dislodgement, or needle-related complications were noted during IONM. Postoperatively, all patients had symmetrical vocal cord movement. Lower EMG amplitudes were observed in older and male patients. Histopathology and laterality showed no significant differences in EMG amplitude. Conclusion: During using TCERM in thyroid surgery, the recording electrodes should be placed contra-laterally on the TC lamina. This approach ensures high and stable EMG signals, which are important for high-quality IONM of the RLN.

Use of Indocyanine Green Fluorescence During Total Thyroidectomy to Identify Parathyroid Glands and Prevent Hypoparathyroidism.

INTRODUCTION: Total thyroidectomy is associated with a high rate of transient or permanent hypoparathyroidism. During surgery, indocyanine green (ICG) fluorescein angiography can be used to detect and preserve well-vascularized parathyroid glands. This technique has been introduced as an intraoperative support to prevent postoperative hypoparathyroidism. MATERIAL AND METHODS: One-hundred consecutive patients who had undergone total thyroidectomy were included in this study. Autofluoroscopy was used on the first dominant side of thyroidectomy and to identify the contralateral parathyroid glands. An intravenous bolus of 5 mg ICG (VERDYE, Diagnostic Green GmbH, Aschheim-Dornacht, Germany) was administered once. ICG fluorescein angiography was used as a "bridge" at the end of the first dominant hemithyroidectomy and after exposure of the parathyroid glands on the second side. This allowed us to (i) determine the vascularization of the first two parathyroid glands and (ii) define the blood vessels and thus the line of dissection of the parathyroid glands of the second resection side. Finally, autofluoroscopy was then applied outside the surgical area on the surgical specimen to assess forgotten parathyroid glands, which should therefore be re-implanted. Autofluoroscopy and ICG fluorescein angiography were evaluated in real time using the same technology, i.e., FLUOBEAM® LX (EUROPE - Fluoptics Grenoble, France; USA - Fluoptics Imaging Inc., Cambridge, MA, USA). The study was approved by the local ethics committee. RESULTS: Autofluorescence and ICG fluorescein angiography were performed without any problems in all cases. A total of 370 parathyroid glands were detected in this series. ICG changed the surgical strategy for the first-side parathyroid glands in 5% of cases, i.e,. they were not well-vascularized and were re-implanted. The rate of transient hypoparathyroidism was 19%. The percentage of parathyroids in the surgical specimen was 3.5% and all were re-implanted during the same surgery. There was no case of postoperative definitive hypoparathyroidism when at least one parathyroid gland with a high fluorescence intensity was preserved on the first side of resection. CONCLUSION: Use of ICG fluorescein angiography may contribute to predicting and thus preventing postoperative definitive hypoparathyroidism after total thyroidectomy. The results of this case series confirm recent studies. Caution is advised when weakly perfused parathyroid glands are discovered.

Administration of neostigmine after tracheal intubation shortens time to successful intraoperative neuromonitoring during thyroid surgery: a randomized controlled trial.

This prospective, randomized controlled trial evaluated the effect of neostigmine for intraoperative neuromonitoring (IONM) during thyroid surgery. Forty subjects undergoing thyroidectomy with IONM, randomized into neostigmine administration after tracheal intubation (Group N, n = 20) or control treatment with normal saline (Group C, n = 20), completed the trial. Electromyography amplitudes of the vagus nerve (V1) were recorded before thyroid dissection. The time from the initial V1 signal check to successful V1 stimulation was recorded. In Group N, all the patients had a successful V1 signal at the first check, whereas ten (50%) patients in Group C had a time delay between the initial V1 check and successful V1 (p < 0.001). The mean delay time among the delayed patients in Group C was 11.2 ± 1.4 min. The mean time from skin incision to successful V1 stimulation was significantly shorter in Group N than in Group C (15.4 ± 2.4 min vs. 19.9 ± 5.7 min, p = 0.003). In Groups N and C, the mean V1 amplitudes were 962.2 ± 434.5 µV vs. 802.3 ± 382.7 µV (p = 0.225), respectively, and the mean R1 amplitudes were 1240.0 ± 836.5 µV vs. 1023.4 ± 455.8 µV (p = 0.316), respectively. There was one bucking event in Group N. In conclusion, neostigmine administration immediately after tracheal intubation can be useful to reverse neuromuscular blockade for successful IONM in thyroid surgeries.

Proposals for Standardization of Intraoperative Facial Nerve Monitoring during Parotid Surgery.

Intraoperative facial nerve monitoring (FNM) has been widely accepted as an adjunct during parotid surgery to facilitate identification of the facial nerve (FN) main trunk, dissection of FN branches, confirmation of FN function integrity, detection of FN injury and prognostication of facial expression after tumor resection. Although the use of FNM in parotidectomy is increasing, little uniformity exists in its application from the literature. Thus, not only are the results of many studies difficult to compare but the value of FNM technology is also limited. The article reviews the current literature and proposes our standardized FNM procedures during parotid surgery, such as standards in FNM setup, standards in general anesthesia, standards in FNM procedures and application of stimulus currents, interpretation of electrophysiologic signals and prediction of the facial expression outcome and pre-/post-operative assessment of facial expressions. We hope that the FNM standardized procedures will provide greater uniformity, improve the quality of applications and contribute to future research.

Investigation of the Electrophysiological and Thermographic Safety Parameters of Surgical Energy Devices during Thyroid and Parathyroid Surgery in a Porcine Model.

In thyroid and parathyroid surgery, surgical energy devices (SEDs) provide more efficient hemostasis than conventional clamp-and-tie hemostasis in areas with rich blood supply. However, when a SED is activated near the recurrent laryngeal nerve (RLN), the heat generated by the SED may injure the nerve irreversibly. To safely apply SEDs in thyroid/parathyroid surgery, this article introduces experimental porcine model studies to investigate the activation and cooling safety parameters of SEDs in standardized electrophysiological (EP) and thermographic (TG) procedures, respectively. In the EP safety parameter experiments, continuous intraoperative neuromonitoring (C-IONM) is applied to demonstrate the RLN function in real-time. The EP activation study evaluates the safe activation distance of SEDs; the EP cooling study evaluates the safe cooling time of SEDs. In the TG safety parameter experiment, a thermal imaging camera is used to record the temperature change after activating the SED. The TG activation study evaluates the lateral thermal spread distance after SED activation in a dry or humid environment and whether smoke and splashing are generated; the TG cooling study evaluates the cooling time. This will help establish the safety parameters of newly developed SEDs used in thyroid/parathyroid surgery and provide safety guidelines to avoid RLN injury and related complications.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

Intraoperative EMG recovery patterns and outcomes after RLN traction-related amplitude decrease during monitored thyroidectomy.

Objectives: Traction injury is the most common type of recurrent laryngeal nerve (RLN) injury in thyroid surgery. Intraoperative neuromonitoring (IONM) facilitates early detection of adverse electromyography (EMG) effect, and this corrective maneuver can reduce severe and repeated nerve injury. This study aimed to evaluate intraoperative patterns and outcomes of EMG decrease and recovery by traction injury. Methods: 644 patients received nerve monitored thyroidectomy with 1142 RLNs at risk were enrolled. Intermittent IONM with stimulating dissecting instrument (real-time during surgical procedure) and trans-thyroid cartilage EMG recording method (without electrode malpositioning issue) were used for nerve stimulation and signal recording. When an EMG amplitude showed a decrease of >50% during RLN dissection, the surgical maneuver was paused immediately. Nerve dissection was restarted when the EMG amplitude was stable. Results: 44/1142 (3.9%) RLNs exhibited a >50% EMG amplitude decrease during RLN dissection and all (100%) showed gradual progressive amplitude recovery within a few minutes after releasing thyroid traction (10 recovered from LOS; 34 recovered from a 51-90% amplitude decrease). Three EMG recovery patterns were noted, A-complete EMG recovery (n=14, 32%); B-incomplete EMG recovery with an injury point (n=16, 36%); C-incomplete EMG recovery without an injury point (n=14, 32%). Patients with postoperative weak or fixed vocal cord mobility in A, B, and C were 0(0%), 7(44%), and 2(14%), respectively. Complete EMG recovery was found in 14 nerves, and incomplete recovery was found in another 30 nerves. Temporary vocal cord palsy was found in 6 nerves due to unavoidable repeated traction. Conclusion: Early detection of traction-related RLN amplitude decrease allows monitoring of intraoperative EMG signal recovery during thyroid surgery. Different recovery patterns show different vocal cord function outcomes. To elucidate the recovery patterns can assist surgeons in the intraoperative decision making and postoperative management.

Necessity of Routinely Testing the Proximal and Distal Ends of Exposed Recurrent Laryngeal Nerve During Monitored Thyroidectomy.

Objectives: Intraoperative neuromonitoring (IONM) is a useful tool to evaluate the function of recurrent laryngeal nerve (RLN) in thyroid surgery. This study aimed to determine the necessity and value of routinely testing the proximal and distal ends of RLN. Methods: In total, 796 patients undergoing monitored thyroidectomies with standardized procedures were enrolled. All 1346 RLNs with visual integrity of anatomical continuity were routinely stimulated at the most proximal (R2p signal) and distal (R2d signal) ends after complete RLN dissection. The EMG amplitudes between R2p and R2d signals were compared. If the amplitude of R2p/R2d ratio reduction (RPDR) was over 10% or loss of signal (LOS) occurred, the exposed RLN was mapped to identify the injured point. Pre- and post-operative vocal cord (VC) mobility was routinely examined with video-laryngofiberscope. Results: Nerve injuries were detected in 108 (8%) RLNs, including 94 nerves with incomplete LOS (RPDR between 13%-93%) and 14 nerves with complete LOS. The nerve injuries were caused by traction in 80 nerves, dissecting trauma in 23 nerves and lateral heat spread of energy-based devices in 5 nerves. Symmetric VC mobility was found in 72 nerves with RPDR ≤50%. The occurrence of abnormal VC mobility (weak or fixed) was 14%, 67%, 100%, and 100% among the different RPDR stratifications of 51%-60%, 61%-70%, 71%-80%, and 81-93%, respectively. Of the 14 nerves with complete LOS, all showed fixed VC mobility. Permanent VC palsy occurred in 2 nerves with thermal injury. Conclusion: Routinely testing the proximal and distal ends of exposed RLN helps detect unrecognized partial nerve injury, elucidate the injury mechanism and determine injury severity. The procedure provides accurate information for evaluating RLN function after nerve dissection and should be included in the standard IONM procedure.

Enhancement of Osteoblast Function through Extracellular Vesicles Derived from Adipose-Derived Stem Cells.

Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cell that is investigated in bone tissue engineering (BTE). Osteoblasts are the main cells responsible for bone formation in vivo and directing ADSCs to form osteoblasts through osteogenesis is a research topic in BTE. In addition to the osteogenesis of ADSCs into osteoblasts, the crosstalk of ADSCs with osteoblasts through the secretion of extracellular vesicles (EVs) may also contribute to bone formation in ADSC-based BTE. We investigated the effect of ADSC-secreted EVs (ADSC-EVs) on osteoblast function. ADSC-EVs (size ≤ 1000 nm) were isolated from the culture supernatant of ADSCs through ultracentrifugation. The ADSC-EVs were observed to be spherical under a transmission electron microscope. The ADSC-EVs were positive for CD9, CD81, and Alix, but ß-actin was not detected. ADSC-EV treatment did not change survival but did increase osteoblast proliferation and activity. The 48 most abundant known microRNAs (miRNAs) identified within the ADSC-EVs were selected and then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO analysis revealed that these miRNAs are highly relevant to skeletal system morphogenesis and bone development. The KEGG analysis indicated that these miRNAs may regulate osteoblast function through autophagy or the mitogen-activated protein kinase or Ras-related protein 1 signaling pathway. These results suggest that ADSC-EVs enhance osteoblast function and can contribute to bone regeneration in ADSC-based BTE.