Background: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. Materials and methods: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at China-Japan Union Hospital. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic curve was used to evaluate predictive efficacy. Results: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2 vs. 40.7%, respectively; P =0.014) and NAR with R1<1400 (77.3 vs. 47.0%, respectively; P =0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 [odds ratio (OR)=2.688, P =0.038], R1<1400 (OR=3.484, P =0.018) as independent risk factors for postoperative temporary VCP. The receiver operating characteristic curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher BMI (OR=1.072, P =0.013), hypertension (OR=1.816, P =0.015), smoking (OR=1.814, P =0.031), and male sex (OR=2.016, P =0.027). Conclusion: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male sex may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

BackgroundPediatric papillary thyroid cancer presents with a more advanced stage of disease than adult PTC; and it is more likely to be aggresive and distant metastases, although the survival rate is high.MethodsA retrospective observational study was performed in children and adults with PTC. Fisher’s exact, chi-square, and rank-sum tests were used to examine the differences. Univariate and multivariate Cox regression analyses were applied to determine the possible risk factors for prognosis. A Kaplan-Meier curve analysis was performed to investigate the relationship between the clinicopathological characteristics and recurrence rate.ResultsThe study involved 156 children and 1,244 adults with PTC. Compared to the group without recurrence, proportions of tumors measuring > 1 cm (48.3% vs. 90.9%) and multifocality (30.3% vs. 63.6%) were higher, N1b stage occurred more frequently (33.8% vs. 100%). However, among adult PTC patients, those with recurrence were older (76.1% vs. 59.4%) than those without recurrence. Risk factors for pediatric PTC recurrence included tumor size and multifocality. However, in adult PTC, the risk factor was LLNM. The newly constructed Stratification.N showed better performance, as illustrated by the fact that patients who were classified into Stratification.N 3 showed an obviously poorer prognosis (P=0.01 and P=0.00062), especially in those aged >14 years (P=0.0052).ConclusionCompared with adult PTC, pediatric PTC showed unique characteristics in terms of clinical pathology and recurrence. Tumor size and multifocality were strong risk factors for pediatric PTC. Accordingly, the novel proposed risk stratification method could effectively predict the recurrence of pediatric PTC.

To examine the putative functions and mechanisms of lysine crotonylation (Kcr) during the development and progression of papillary thyroid cancer (PTC). Samples of thyroid cancer tissues were collected and subjected to liquid chromatography–tandem mass spectrometry. Crotonylated differentially expressed proteins (DEPs) and differentially expressed Kcr sites (DEKSs) were analyzed by Motif, dynamic expression model analysis (Mfuzz), subcellular localization, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, Go Ontology (GO) annotation, and protein–protein interaction analysis (PPI). Validation was performed by immunohistochemistry (IHC). A total of 262 crotonylated DEPs and 702 DEKSs were quantitated. First, for the tumor/normal comparison, a dynamic expression model analysis (Mfuzz) of the DEKSs revealed that clusters 1, 3, and 4 increased with the progression of thyroid cancer; however, cluster 6 showed a dramatic increase during the transition from N0-tumor to N1-tumor. Furthermore, based on GO annotation, KEGG, and PPI, the crotonylated DEPs were primarily enriched in the PI3K-Akt signaling pathway, Cell cycle, and Hippo signaling pathway. Of note, crosstalk between the proteome and Kcr proteome suggested a differential changing trend, which was enriched in Thyroid hormone synthesis, Pyruvate metabolism, TCA cycle, Cell cycle, and Apoptosis pathways. Similarly, for the LNM comparison group, the DEKSs and related DEPs were primarily enriched in Hydrogen peroxide catabolic process and Tight junction pathway. Finally, according to The Cancer Genome Atlas Program (TCGA) database, the differential expression of Kcr DEPs were associated with the prognosis of thyroid cancer, indicating the prognostic significance of these proteins. Moreover, based on the clinical validation of 47 additional samples, Kcr was highly expressed in thyroid tumor tissues compared with normal tissue (t = 9.792, P < 0.001). In addition, a positive correlation was observed between Kcr and N-cadherin (r = 0.5710, P = 0.0015). Moreover, N-cadherin expression was higher in the relatively high Kcr expression group (χ2 = 18.966, P < 0.001). Higher Kcr expression was correlated with thyroid tumorigenesis and lymphatic metastasis, which may regulate thyroid cancer progression by Pyruvate metabolism, TCA cycle, Cell cycle, and other pathways.

Bacterial keratitis (BK) is one of the most threatening ocular diseases, leading to stromal injury, corneal perforation, or even blindness. Avoiding side effect is necessary for efficient BK treatment. Herein, we develop GDY-Ag@AgCl heterojunction catalysts to achieve BK treatment via mild phototherapy strategy. Mild photothermal therapy (PTT) can greatly enhance the generation of ROS produced by photocatalytic therapy (PCT), which can decrease the dosage of photosensitizer, as well as solve the issue of uncontrolled local overheating and the accumulation of PTT agents, minimizing side effects and avoiding secondary injuries. The results demonstrate that lower dosage of PTT/PCT agents, and milder and controlled thermal effect of GDY-Ag@AgCl exhibits excellent inactivation performance against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, this phototherapy strategy not only achieves more effective treatment of BK induced by MRSA with no side effects but also shows a superior ability to alleviate inflammation. This strategy offers a safe and promising theragnostic approach for treating ocular drug-resistant bacterial infections.

Background Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. Methods Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. Results PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited “hot” tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). Conclusions PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

Objective:To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. Methods:Case information of 8340 thyroid cancer patients hospitalized at China-Japan Union Hospital of Jilin University, Jilin Province, China, in the Thyroid Surgery Department from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a chi 2 test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by receiver operating characteristic, calibration curves, and Decision curve analysis. Results:The strengthening the reporting of cohort, cross-sectional, and case-control studies in surgery (STROCSS) guideline was followed to conduct a retrospective cohort study. A total of 8340 patients, including 1817 (21.8%) men and 6523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland (P=0.042), ultrasound showing a maximum nodal diameter >1 cm (P=0.002), multifocal carcinoma (P<0.001), invasion of surrounding tissue (P=0.005), lymph node metastases in the central compartment (P=0.034), lateral cervical lymph node metastasis (P<0.001), and prolonged operation (P<0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR=1.411, P=0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR=1.532, P=0.013, 95% CI: 1.095-2.144), and duration of surgery (OR=1.009, P<0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. Conclusion:High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

BackgroundDespite improvements in overall survival, the recurrence of differentiated thyroid cancer (DTC) is becoming more common and remains a challenge necessitating accurate reappraisal of the patient. This study aimed to describe the characteristics, reasons, morbidity, and strategies of second operations for DTC.MethodsThis was a retrospective observational study of patients with DTC who underwent a second surgery between June 2008 and June 2021 in the Department of Thyroid Surgery at China–Japanese Union Hospital, Jilin University, P.R. China. All clinical characteristics were recorded, and the analysis was estimated using SPSS.ResultsSecond surgeries were detected in 683 patients. The proportion of second operations changed with the update of international guidelines from 2015 (P < 0.001). The true recurrence rate progressively increased from 21.3% to 61.5%. The rate of an “absence of preoperative FNA” or an “absence of intraoperative pathology at first surgery” decreased from 49.8% to 12.7%, while that of a “misdiagnosis of preoperative FNA at second surgery” decreased from 10% to 1.8%. The most common tumor location during the second surgery was the lateral lymph nodes (n = 104, 36.5%), with a median time to relapse of 36 months. Completion of thyroidectomy and lymph node dissection correlated with the second operation.ConclusionAfter 2015, second surgeries were more standardized, the incidence of complications decreased, and real recurrence became the most common reason for a second DTC surgery.

Objective:To investigate the feasibility and advantages of unilateral primary hyperparathyroidism (PHPT) treated by transthyretal interosseous muscle approach surgery.Methods:Clinical data of 7 patients with unilateral PHPT treated by interstitial sternocleidomastoid muscle approach from Jan. 2021 to Feb. 2022 in the thyroid surgery of China-Japan Union Hospital of Jilin University were retrospectively analyzed, including preoperative blood calcium concentration, operation time, incision length, intraoperative parathyroid hormone (PTH) , blood calcium concentration and PTH value in the first month after surgery, abnormal sensation of the skin in the anterior cervical area, etc. The feasibility and advantages of interstitial sternocleidomastoid muscle approach surgery for unilateral PHPT were analyzed.Results:All 7 patients with unilateral PHPT were operated successfully. The PTH was 17.2-63.3 pg/ml on recheck 1 month after surgery, which were all within the normal range. The time from skin opening to resection of the diseased parathyroid gland was 20-35 min, and the length of the surgical incision was 3-4 cm. all patients were given intravenous and oral calcium therapy after surgery, and the blood calcium and PTH levels were within the normal range at 3-12 months of follow-up; the incision recovered well, and there was no significant sensory and functional abnormalities in the anterior neck area.Conclusion:The treatment of unilateral PHPT through the sternocleidomastoid interosseous approach can ensure the safety and efficacy of the operation while better protecting the sensory and motor functions of the anterior cervical region and improving the aesthetics of the surgical incision.

BackgroundCuprotosis is a newly discovered form of cell death that differs from other types of cell death. The aim of this study was to investigate the functional role and a possible prognostic model for thyroid cancer.MethodsTCGA and GEO were used to investigate the differential expression of CRGs in THCA. KEGG and GO enrichment analyses were applied to investigate the possible molecular functions. The features of CRGs were selected by LASSO regression. 20 pairs of samples were randomly collected from the hospital to compare expression between tumor and normal.ResultsAmong the 19 CRGs related to thyroid cancer recurrence, 16 genes were differentially expressed in thyroid cancer. KEGG analysis showed that the 19 CRGs were mainly enriched in cell death, cell cycle and ribosomal pathways. K-M survival analysis and subsequent multiple logistic regression revealed that the expression of BUB1 and GINS2 were potential risk factors for disease-free survival (DFS) of thyroid cancer. In addition, further LASSO-regression selected the following three DFS-related CRGs: FDX1, BUB1 and RPL3. A novel prognostic prediction model was constructed by nomogram, and the prediction probability for 1-, 3- and 5-year survival approached the actual time. As for the possible mechanisms, FDX1, BUB1 and RPL3 were associated with immune infiltration. The cell model experiment illustrated that the ATM signaling pathway might be involved in thyroid cancer cell death.ConclusionThree CRG models (FDX1, BUB1, RPL3) could better predict the prognosis of thyroid cancer. Immune cell infiltration and the ATM pathway were the possible mechanisms.

Background:Medullary thyroid carcinoma (MTC) patients have poor survival, tumor/node/metastasis (TNM) stage and biochemical prognosis are the most important factors. We investigated the clinical significance of calcitonin (Ctn) to assess the biochemical prognosis of MTC.Methods:This retrospective observational study enrolled 77 MTC patients with complete information and primary surgery at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University between 2009 and 2020. Patient and MTC characteristics were recorded. All patients were divided into remission, stable, and progression according to biochemical prognosis. We analyzed the correlation between preoperative serum Ctn, TNM stage and biochemical prognosis.Results:Elevated preoperative serum Ctn was positively correlated with TNM stage. Patients with higher Ctn, multifocality, and bilateral tumors were associated with a higher TNM stage. Multivariate logistic regression analysis showed that preoperative serum Ctn level was an independent risk factor for TNM stage. Receiver operating characteristic (ROC) analysis found the best Ctn cut-off value for predicting TNM III was 45.88 pg/mL, which had a sensitivity of 87.2% and a specificity of 65.8%. The best Ctn cut-off value for predicting TNM IV was 167.00 pg/mL, with a sensitivity of 92.9% and a specificity of 77.6%. In univariate analysis, patients with higher preoperative serum Ctn, multifocality, bilateral tumors, and higher TNM stage were more likely to progress. The optimal cut-off value for progression was 195.5 pg/mL, which had a sensitivity of 80.0% and a specificity of 70.2%. For every 1-unit increase in preoperative serum Ctn levels, the risk of progression increased by 1.004 times (P=0.008), and patients with TNM stage III [hazard ratio (HR) =9.663; 95% confidence interval (CI): 1.411, 66.156] were nearly 9.7-fold more likely to progress than those in TNM stage I/II.Conclusions:Elevated preoperative serum Ctn predicted poor clinical outcomes in MTC.

Background Thyroid surgery is increasingly demanding in terms of cosmetic neck outcomes and protection of anterior neck function, so we have adopted an alternative sternocleidomastoid intermuscular approach (SMIA) for open/conventional thyroidectomy. The protection of recurrent laryngeal nerve (RLN) and external branch of superior laryngeal nerve (EBSLN) is the key and difficult point in thyroid surgery. The aim of this study was to testify the feasibility of RLN and EBSLN functional protection during SMIA thyroidectomy with the intraoperative neuromonitoring. Methods A total of 39 patients and 39 RLN and EBSLNs who underwent monitored SMIA thyroidectomy were included. Thyroid gland is revealed and excised anterior to the cervical sheath between the sternal and clavicular heads of the sternocleidomastoid muscle. Standardized intraoperative neuromonitoring (IONM) procedures and postoperative laryngeal examination were performed to audit the SMIA. Following the four-step method, V1, R1, R2, and V2 were monitored and the signal values were recorded. Statistical analysis was used to evaluate the change of IONM amplitude of RLN, combined with the results of laryngoscopy before and after operation to determine the status of RLN. EBSLN injuries were identified from changes in cricothyroid muscle (CTM) twitch and EMG. SMIA video vignette is detailed. Results All RLN and EBSLNs [17 on the left and 22 on the right] were monitored in 39 patients [5 men, 34 women; mean age 34.1±8.7 years; mean body mass index 22.5 (±3.0, 17.0–30.8) kg/m2] undergoing SMIA. For RLN of the affected side, we compared the V2 and V1 (1,236±672 vs. 1,240±428, P=0.973), R2 and R1 (1,676±778 vs. 1,656±765, P=0.849) signals separately, and the results were not statistically different (P>0.05). Comparing the V1 (1,240±428 vs. 1,309±395, P=0.601) signals of the bilateral recurrent laryngeal nerve, there was no statistical difference (P>0.05). CTM twitch and EMG were preserved. Conclusions The SMIA technique appears feasible. RLN and EBSLN are easier to be exposed during thyroid surgery of SMIA, which is beneficial to the neuroprotection during the operation. At the same time, it can protect the anterior cervical function and improve the cosmetic effect after operation.

Background Lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and fibrinogen (FIB) have been identified as predictive biomarkers in several malignancies. The aim of this study was to explore the association between inflammatory index with clinicopathologic features as well as recurrence risk in intermediate-to high-risk papillary thyroid carcinoma (PTC). Methods Retrospective evaluation of 212 patients diagnosed with intermediate-to high-risk PTC who underwent surgery at China-Japan Union Hospital between 2015 and 2016. Logistic regression and receiver operating curves (ROC) were used to explore possible risk factors. Results LMR was predictive of capsular invasion (AUC=0.595, P =0.017), FIB was predictive of lymph node metastasis (LN) (AUC=0.714, P =0.002), MPV was predictive of largest LN size ≥1cm (AUC=0.639, P =0.002), PLR and MPV were predictive of recurrence (AUC=0.616, P =0.032; AUC=0.626, P =0.020). In addition, FIB ≤ 2.6 (OR=6.440, 95%CI:1.777-23.336, P =0.005) and capsular invasion (OR=3.773, 95%CI:1.171-12.159, P =0.026) were identified as independent risk factors for lymph node metastasis by multivariate analysis. In addition, LN metastasis ( P =0.048), largest LN size ≥ 1 cm ( P =0.032), MPV > 9.4 ( P =0.046), and PLR ≤ 128.1 ( P =0.032) were significantly related with recurrence. Further multivariate regression analysis revealed that PLR ≤ 128.1 was a potentially independent risk factor for recurrence. Specifically, the risk of recurrence was 2.951 times higher in patients with a PLR ≤ 128.1 compared with patients with a PLR > 128.1 (OR=2.951, 95% CI:1.238-7.037, P =0.015). Conclusion In intermediate-to high-risk PTC, LMR, PLR, MPV, and FIB could predict clinicopathologic features and recurrence, with lower PLR being the potential risk factors for recurrence.

Introduction and ObjectiveThere is a need for a simplified technique for C-IONM in robotic surgery. The primary aim of this study was to describe our clinical experience with the use of percutaneous C-IONM in robotic bilateral axillary thyroid surgery.MethodsThis study prospectively enrolled 304 consecutive patients who underwent robotic thyroidectomy via the bilateral axillo-breast approach and standardized C-IONM via percutaneous probe stimulation.Results323 RLNs were analyzed. C-IONM with percutaneous probes was feasible in all cases. During this study, we did not record any cases of probe displacement, and no additional robotic maneuvers were required. The average stimulation intensity was 2 mA. There were no adverse local or systemic C-IONM side effects. The mean time required for probe positioning was 3 minutes. The EMG amplitude signal of 48 RLNs decreased significantly, < 50% from the original V1 signal. In these cases, the surgical procedure was modified.ConclusionThe proposed percutaneous C-IONM provides a simplification of the continuous monitoring procedure for robotics. The advantage of percutaneous C-IONM is that it does not require additional trocar space, repeated instrument changes, and unmodified cosmesis. To our knowledge, this is the first study on the application of percutaneous C-IONM in robotic thyroid surgery.

Purpose: This study examined the clinicopathological characteristics of 6279 N1 differentiated thyroid cancer (DTC) patients who underwent operations in our center. Methods: This was a retrospective longitudinal analysis. We categorized the DTC patients on the basis of various lymph node (LN) characteristics. Logistic regression models and multiple linear regression models were used for the correlation analysis. Results: A total of 3693 (58.8%) N1a patients and 2586 (41.2%) N1b patients were included. Patients with N1b disease had larger metastatic foci (0.5 vs 0.15 cm), a greater number of metastatic LNs (5 vs 2), a greater number of dissected LNs (25 vs 7), and a smaller lymph node ratio (NR, number of positive LNs/number of sampled LNs) (23.1% vs 28.6%) than patients in stage N1a. Comparing the clinicopathological features, we found that male, increased tumor size, multifocality, and thyroiditis increased the risk of stage N1b disease (P < 0.05). Sex, multifocality, capsular infiltration, and tumor size were associated with the size of the metastatic LNs (P < 0.05). Sex, capsular infiltration, and nodular goiter were associated with the NR (P < 0.05). Female sex, tumor located in inferior lobe, maximal tumor diameter (MTD) < 1 cm, and nodular goiter were independent predictors for skip metastases (P < 0.05). MTD > 1 cm, central neck metastasis and age were independent predictors for bilateral la teral neck metastasis (BLNM) (P < 0.05). Conclusion: The LN characteristics of stage N1a and N1b disease were associated with significantly different features, such as sex, tumor size, multifocality, capsular infiltration, and nodular goiter.

Purpose The institutional database of the Thyroid Surgery Division in China–Japan Union Hospital of Jilin University was queried to audit time trend patterns in thyroid cancer (TC) management between 2008 and 2017. Methods Retrospective longitudinal analysis. Clinicopathological features and treatment strategies were analyzed. Frequencies and multivariate tests were used to detect correlations. Results Clinical data were obtained from 15,000 TC patients (i.e., 71.3% of 21,044 operations). Papillary was the most common histological subtype ( n = 14,916, 99%), and 76% were microcarcinomas. Stage I (95%) and low-risk patients (58%) were prevalent throughout the 10-year period. The trend for total thyroidectomy increased from 29.1% (2008–2012) to 67.9% (2013–2015), and then dropped to 48.6% (2016–2017). A total of 8827 (52%) patients received central lymph node dissection (CLND). The tendency for CLND increased from 15.7 to 86.4% during the 10-year period. While the trend of lateral lymph node dissection decreased from 71.3 to 13.3%. Radioactive iodine therapy was offered to 10% of patients (2008–2012), except for a low value (5.4%) in 2009, and then increased from 12.3% (2012) to 41.3% (2015), while decreased to 32.4% (2017). Conclusion The surgical management of TC patients has undergone continuous changes over the past 10 years. The evolution from aggressive treatment to a more conservative approach has been constant. Our results suggest that the current surgical management approach for TC is adequate and in support of the published guidelines. Our findings warrant further investigation to determine the clinical implications of decision making for TC.