Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer.

OBJECTIVE: To compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC. METHODS: A total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups. RESULTS: Of the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037). CONCLUSION: Although preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.

Practical multi-class event classification approach for distributed vibration sensing using deep dual path network.

Influenced by severe ambient noises and nonstationary disturbance signals, multi-class event classification is an enormous challenge in several long-haul application fields of distributed vibration sensing technology (DVS), including perimeter security, railway safety monitoring, pipeline surveillance, etc. In this paper, a deep dual path network is introduced into solving this problem with high learning capacity. The spatial time-frequency spectrum datasets are built by utilizing the multidimensional information of DVS signal, especially the spatial domain information. With the novel datasets and a high-parameter-efficiency network, the proposed scheme presents good reliability and robustness. The feasibility is verified in an actual railway safety monitoring field test, as a proof-of-concept. Seven types of real-life disturbances were implemented and their f1-scores all reached up to 97% in the test. The performance of this proposed approach is fully evaluated and discussed. The presented approach can be employed to improve the performance of DVS in actual applications.

Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression.

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na(+)/I(-) symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC).

Association of serum 25-hydroxyvitamin D levels with aggressiveness of papillary thyroid cancer.

Objective: Serum 25-hydroxyvitamin D (25(OH)D) deficiency has been known to be associated with the risk and mortality of several cancers. However, the role of 25(OH)D in papillary thyroid cancer (PTC) remains controversial. This study aimed to investigate the association between 25(OH)D and clinicopathologic features of PTC. Methods: Patients who underwent thyroidectomy were retrospectively reviewed. Serum 25(OH)D levels were measured within a week prior to surgery. The patients were categorized into four quartiles according to season-specific 25(OH)D levels. The association between 25(OH)D levels and clinicopathologic features of PTC was analyzed. Results: A total of 2932 patients were enrolled in the study. The 25(OH)D levels were significantly higher in patients with lymph node metastasis (LNM; P < 0.001), lateral LNM (P < 0.001), and multifocal tumors (P < 0.001). Compared to the first quartile (Q1) of 25(OH)D level, the third quartile (Q3) and the fourth quartile (Q4) showed an unadjusted OR of 1.36 (95% CI: 1.09-1.69; P = 0.006) and 1.76 (95% CI: 1.42-2.19; P < 0.001) for LNM (P for trend < 0.001), respectively. An increased risk of multifocal tumors was strongly associated with high 25(OH)D concentration (P for trend <0.001). Similar results were obtained after adjusting for confounding factors. Conclusion: High 25(OH)D levels are associated with aggressive features of PTC, such as lymph node metastasis and multifocality.

Single-Cell Transcriptome Analysis Reveals Inter-Tumor Heterogeneity in Bilateral Papillary Thyroid Carcinoma.

Background: The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and the phenotype of cells within the TME in bilateral PTC are poorly understood. Methods: We performed unbiased transcriptome-wide single-cell RNA sequencing (scRNA-seq) analysis on 29,561 cells from 3 pairs of bilateral PTC and 1 non-tumor thyroid sample. The results of the analysis were validated by a large-scale bulk transcriptomic dataset deposited in The Cancer Genome Atlas (TCGA) database. Results: Our integrative analysis of thyroid follicular cells revealed 42 signaling pathways enriched in malignant follicular cells, including cytokine-cytokine receptor interaction, PI3K/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. A 6-gene signature (CXCL3, CXCL1, IL1A, CCL5, TNFRSF12A, and IL18) in the cytokine-cytokine receptor interaction pathway was constructed to predict the prognosis of patients with PTC, with high risk scores being associated with decreased overall survival [hazard ratio (HR) = 3.863, 95% CI = 2.233-6.682, p < 0.001]. Gene set variation analysis (GSVA) indicated that the pathways enriched in bilateral PTC were significantly different, indicating great heterogeneity in bilateral PTC, even with the same BRAF V600E mutation. Comprehensive analysis of T cells revealed that the proportion of CD8+ tissue-resident memory T cells expressing IFNG decreased in tumor samples with advanced N stage. Within the myeloid compartment, the ratio of suppressive M2-like to pro-inflammatory M1-like macrophages increased with advanced disease stage, which was confirmed in the bulk dataset using transcriptomic profiles. In addition, we also identified numerous biologically critical interactions among myeloid cells, T cells, and follicular cells, which were related to T-cell recruitment, M2-like macrophage polarization, malignant follicular cell progression, and T-cell inhibitory signaling. Conclusion: Our integrative analyses revealed great inter-tumor heterogeneity within the TME in bilateral PTC, which will offer assistance for precise diagnosis and treatment.

Total thyroidectomy vs thyroid lobectomy for localized medullary thyroid cancer in adults: A propensity-matched survival analysis.

BACKGROUND: This study aimed to clarify whether the extent of thyroidectomy (total thyroidectomy vs thyroid lobectomy) influences survival in adults with localized medullary thyroid cancer. METHODS: Patients with localized medullary thyroid cancer were identified using the Surveillance, Epidemiology, and End Results database (2000-2018). An independent cohort of patients with localized medullary thyroid cancer were retrospectively reviewed from three medical centers in China from 2010 to 2020. The patients were grouped by the extent of surgery (total thyroidectomy vs thyroid lobectomy). Primary end points were overall survival and disease-specific survival. RESULTS: From 1,686 patients with medullary thyroid cancer identified in SEER, 1,122 patients met inclusion for matching, with a median follow-up of 99 months. After propensity score matching, 122 patients underwent a total thyroidectomy and 122 patients underwent a thyroid lobectomy. The 10-year overall survival was 85.2% (77.9%-90.7%) and 83.1% (75.5%-90.7%) in total thyroidectomy group and in thyroid lobectomy group, respectively. The 10-year disease-specific survival was 100% and 96.8% (93.1%-100%) in total thyroidectomy group and in thyroid lobectomy group, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with localized medullary thyroid cancer undergoing total thyroidectomy or thyroid lobectomy (hazard ratio = 0.83, 95% confidence interval 0.44-1.57, P = .57 and hazard ratio = 0.49, 95% confidence interval 0.10-2.41, P = .39, respectively). Forty-seven patients with localized medullary thyroid cancer were identified in an independent Chinese cohort (n = 29 in total thyroidectomy group vs n = 18 in thyroid lobectomy group). After a median follow-up of 47 months, there was no mortality observed in either group. CONCLUSION: This study suggests that the extent of thyroidectomy does not influence survival for patients with early-stage localized medullary thyroid cancer and that thyroid lobectomy might be adequate in this patient population.

Efficacy and safety of targeted therapeutics for patients with radioiodine-refractory differentiated thyroid cancer: Systematic review and network meta-analysis.

Background: Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to achieve long-term survival. Methods: A systematic search of the PubMed, Embase, and ClinicalTrials.gov databases was conducted to identify eligible randomized controlled trials (RCTs) comparing the efficacy and safety of targeted treatments for patients with RAIR-DTC from inception to April, 2022. Data were extracted by following the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. We calculated the odds ratio (OR) or hazard ratio (HR), its corresponding 95% credible intervals (CrI), and the surface under the cumulative ranking curve (SUCRA) to indicate ranking probability using Bayesian network meta-analyses. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events. Results: A total of 12 eligible RCTs involved 1,959 patients and 13 treatments: apatinib, cabozantinib, anlotinib, nintedanib, lenvatinib, lenvatinib with low dose (LD), sorafenib, sorafenib plus everolimus, donafenib (200 mg), donafenib (300 mg), pazopanib (continuous), pazopanib (intermittent), and vandetanib. Pooled analyses indicated that targeted therapeutics significantly prolonged PFS and OS in patients with RAIR-DTC (0.31, 0.21-0.41; 0.69, 0.53-0.85, respectively) compared with placebo. Network meta-analyses indicated that lenvatinib showed the most favorable PFS, with significant differences versus sorafenib (0.33, 0.23-0.48), vandetanib (0.31, 0.20-0.49), nintedanib (0.30, 0.15-0.60), and placebo (0.19, 0.15-0.25), while apatinib was most likely to be ranked first for prolonging OS with a SUCRA of 0.90. Lenvatinib showed the highest ORR (66%, 61%-70%), followed by anlotinib (59%, 48%-70%) and apatinib (54%, 40%-69%). Lenvatinib caused the most adverse events of grade 3 or higher, followed by lenvatinib (LD) and apatinib. Different toxicity profiles of individual treatment were also revealed. Conclusion: This network meta-analysis suggests that lenvatinib and apatinib were associated with the best progression-free survival and overall survival benefits, respectively, for patients with RAIR-DTC, compared with other targeted therapeutics. Patients who received lenvatinib or apatinib also had more grade 3 or higher adverse events. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=302249], identifier [CRD42022302249].

Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

OBJECTIVE: Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy. DESIGN: Prospective randomized laboratory investigation. SETTING: University research laboratory. SUBJECTS: A total of 268 male Long Evans rats. INTERVENTIONS: Post-cardiac-arrest therapeutic hypothermia. MEASUREMENTS AND MAIN RESULTS: Adult male Long Evans rats that achieved return of spontaneous circulation after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37°C ± 1°C) or therapeutic hypothermia (33°C ± 1°C) initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation and maintained for 24 or 48 hrs. Therapeutic hypothermia initiated 0, 1, 4, and 8 hrs after return of spontaneous circulation resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14%, respectively, compared to 17% for normothermic controls and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0%, respectively, compared to 2% for normothermic controls (*p < .05 vs. normothermia). These outcomes were not different when therapeutic hypothermia was maintained for 24 vs. 48 hrs. In contrast, hippocampal CA1 pyramidal neuron counts were 53% ± 27%*, 53% ± 19%*, 51% ± 24%*, and 65% ± 16%* of normal, respectively, when therapeutic hypothermia was initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation compared to 9% in normothermic controls (*p < .01 vs. normothermia). Furthermore, surviving neuron counts were greater when therapeutic hypothermia was maintained for 48 hrs compared to 24 hrs (68% ± 15%* vs. 42% ± 22%, *p < .0001). CONCLUSIONS: In this study, post-cardiac-arrest therapeutic hypothermia resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4 hrs after return of spontaneous circulation. However, histologic assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when therapeutic hypothermia was maintained for 48 vs. 24 hrs.

Effect of Tumor Location on the Risk of Bilateral Central Lymph Node Metastasis in Unilateral 1-4 cm Papillary Thyroid Carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC) has a high incidence of lymph node metastasis (LNM). Our aim was to determine whether tumor location is a useful feature to predict bilateral central lymph node metastasis (CLNM) in unilateral 1-4 cm PTC. PATIENTS AND METHODS: Data on unilateral 1-4 cm PTC patients from 2016 to 2019 were collected retrospectively. The clinical and pathological characteristics of the tumors and lymph nodes were analyzed statistically. RESULTS: The mean patient age was 49.1±12.3 (23-73) years, and the majority were women (n=1334, 75.4%). A total of 1767 patients were analyzed, and 256 (14.5%) had bilateral CLNM. Tumor location was an independent risk factor in predicting bilateral CLNM (p<0.001). The odds of bilateral CLNM were the highest in the near isthmus (OR 6.452, 95% CI: 3.658-11.379, p<0.001). In a multivariate regression model adjusting for other risk factors, near-isthmus tumors had the highest risk of bilateral CLNM (OR 7.319, 95% CI: 3.844-13.933, p<0.001), followed by lower lobe tumors (OR 2.338, 95% CI: 1.315-4.155, p=0.004) and middle lobe tumors (OR 1.845, 95% CI: 1.035-3.291, p=0.038), compared to upper lobe tumors. CONCLUSION: Tumor location is an independent risk factor in predicting the risk of bilateral CLNM. Near-isthmus tumors carry the highest risk of bilateral CLNM.

Increased thyroid malignancy in patients with primary hyperparathyroidism.

BACKGROUND: Multiple studies have reported the increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer. METHODS: Medical records of consecutive patients with PHPT (n = 318) were reviewed from January 2010 to September 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed. RESULTS: Of a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR = 2.13, 95% CI: 1.13-3.99, P = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR = 0.50, 95% CI: 0.26-0.93, P = 0.028). CONCLUSION: In conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.

Recurrent Laryngeal Nerve Injury Near the Nerve Entry Point in Total Endoscopic Thyroidectomy: A Retrospective Cohort Study.

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) still occurs in total endoscopic thyroidectomy (TET) by using intraoperative neuromonitoring (IONM). As the region where most injuries occur, more attention should be paid to RLNI near the nerve entry point (NEP) in TET. MATERIALS AND METHODS: This cohort study collected retrospectively data from 415 patients who underwent TET between February 2012 and December 2019. The functions of the recurrent laryngeal nerve (RLN) in TET were recorded by IONM. The patients with RLNI near the NEP were followed up by laryngoscopies. The demographic and clinical characteristics, the mechanisms of RLNI, and the outcomes of RLNI were recorded and analyzed. RESULTS: There were a total of 444 at-risk nerves in 405 patients were analyzed. The incidence of RLNI near the NEP was 7.9%. RLNs with extralaryngeal branches were more likely to be injured near the NEP (P = 0.037). The incidences of different types of RLNI, in order of frequency, were 68.8% for thermal injury (n = 22), 28.1% for traction/compression injury (n = 9), and 3.1% for transverse injury (n = 1). A total of 93.8% (n = 30) of RLNI patients had complete recovery of vocal cord activity function. CONCLUSION: The extralaryngeal branch was a risk factor for RLNI near the NEP in TET. Thermal injury caused by an ultrasonic scalpel was the most common cause of RLNI near the NEP. Most RLNIs near the NEP would eventually recover.

Mechanisms of recurrent laryngeal nerve injury near the nerve entry point during thyroid surgery: A retrospective cohort study.

BACKGROUND: The use of intraoperative neuromonitoring (IONM) for visual identification of recurrent laryngeal nerve (RLN) has decreased the rates of RLN injury (RLNI) during thyroid surgery. However, little attention has been paid to RLNI near the nerve entry point (NEP), where most injuries occur. The aim of this study was to determine the mechanism of RLNI near the NEP and to describe the recovery of nerve function. METHODS: Patients undergoing thyroid surgery were analyzed to identify true loss of signal (LOS) by IONM. Follow-up for vocal cord palsy (VCP) was confirmed by a postoperative laryngoscopy. The risk factors for RLNI, the type of RLNI, the prevalence of VCP and the time for VCP recovery were all recorded and analyzed. RESULTS: We analyzed 3582 at-risk nerves in 2257 surgical patients. The overall rate of RLNI near the NEP in at-risk nerves was 3.2%. RLNI was more likely to occur in nerves with extralaryngeal bifurcation (p = 0.013). The distribution of RLNI types, in order of frequency, was traction (52.6%; n = 61), compression (38.8%; n = 45), thermal (7.8%; n = 9), and nerve transection (0.9%; n = 1). Complete recovery from VCP was documented in 93.1% (n = 108) of RLNI. CONCLUSION: Patients with a bifurcated RLN were at a higher risk of RLNI near the NEP than those without bifurcation. Traction and compression injuries occurred most frequently, but would eventually recover. Excessive stretching of the thyroid lobe played a role in RLNIs near the NEP.

The Extent of Therapeutic Central Compartment Neck Dissection in Unilateral cT1N1a or cT2N1a Papillary Thyroid Carcinoma.

PURPOSE: Papillary thyroid carcinomas (PTCs) frequently metastasize to the central neck compartment. Therapeutic central compartment neck dissection (CCND) is a well-established treatment for PTC nodal metastases; however, the extent to which therapeutic CCND should be performed remains controversial. In this study, we investigated the predictive risk factors for contralateral paratracheal lymph node metastasis (LNM) in unilateral cT1N1a or cT2N1a PTC. PATIENTS AND METHODS: In this case-control study, which was conducted at a single center, demographic and pathological data from unilateral cT1N1a or cT2N1a PTC patients were collected from January 2017 to March 2019. All patients were treated with total thyroidectomy and bilateral CCND. RESULTS: Two hundred thirty-seven patients met the inclusion criteria. Forty-nine patients (20.7%) were diagnosed with positive lymph nodes in the contralateral paratracheal region. Male sex (p=0.003), T2 disease (21-40 mm) (p<0.001), inferior pole tumor (p=0.011), near isthmus tumor (p<0.001), aggressive pathology (p<0.001), intraglandular dissemination (p=0.009), pretracheal LNM (p<0.001), >5 metastatic lymph nodes (p<0.001) and extranodal invasion (p=0.003) were significantly associated with contralateral paratracheal LNM in univariate analysis. Multivariate analysis showed that male sex (p=0.005, OR=17.545), T2 disease (p=0.003, OR=34.317), inferior pole tumor (p=0.022, OR=8.289), near isthmus tumor (p=0.001, OR=40.229), aggressive pathology (p=0.027, OR=48.063), pretracheal LNM (p=0.002, OR=14.235) and >5 metastatic lymph nodes (p=0.025, OR=23.426) were independent risk factors for contralateral paratracheal LNM. CONCLUSION: Male sex, T2 disease, a tumor located near the isthmus or inferior pole, aggressive pathology, pretracheal LNM and >5 metastatic lymph nodes were predictive factors for contralateral paratracheal LNM in unilateral cT1N1a or cT2N1a PTC. These data may be useful to identify targets for surveillance or develop therapeutic interventions for patients with CCND.

Predicting factors for central or lateral lymph node metastasis in conventional papillary thyroid microcarcinoma.

BACKGROUND: Optimal management for papillary thyroid microcarcinoma (PTMC) remains controversial. The purpose of this study was to explore risk factors predictive of cervical lymph node metastasis in conventional PTMCs. METHODS: Conventional PTMC patients (n = 2,404) undergoing surgery between 2010 and 2017 were grouped and analyzed according to the positivity of cervical lymph node. RESULTS: Central lymph node (CLN) metastases and lateral lymph node (LLN) metastases were observed in 915 (38.1%) and 184 (7.7%) cases, respectively. Multivariate analysis found that male (odds ratio [OR] = 1.974, p < 0.001), younger age (OR = 1.601, p < 0.001), tumor size (OR = 1.935, p < 0.001), extrathyroidal extension (ETE) (OR = 1.647, p < 0.001), multifocality (OR = 1.416, p < 0.001), and intrathyroidal spreading (OR = 3.355, p < 0.001) predicted increased CLN metastasis. In particular, younger age, multifocality, and intrathyroidal spreading were significantly associated with a high number of CLN metastases (n ≥ 5). The presence of CLN metastasis was strongly associated with LLN metastasis (OR = 5.426, p < 0.001). CONCLUSION: Male, younger age, tumor size, ETE, multifocality, and intrathyroidal spreading predict increased CLN metastasis in PTMCs. In patients with suspicious lateral lymphadenopathy, the presence of CLN metastasis is independently associated with LLN metastasis.

Subplatysmal or subfascial approach in totally endoscopic thyroidectomy has better postoperative efficacy for voice, sensory, swallowing symptoms and cosmetic result. Cohort study.

BACKGROUND: After totally endoscopic thyroidectomy (TET), patients usually suffer from voice, sensory, swallowing symptoms and they are also concerned with the postoperative cosmetic result. We compared the effects of subfascial dissection method with the subplatysmal method in TET on postoperative symptoms and cervical appearance. METHODS: 143 female patients who underwent totally endoscopic thyroid surgery were assigned to the subplatysmal approach group and subfascial approach group. The patient's voice symptoms were assessed using the Voice Handicap Index (VHI) questionnaire. Sensory function was assessed with subjective pain and light touch sensation. Swallowing symptoms were assessed using the Swallow Impairment Score (SIS) questionnaire and the 3 oz water swallow test. Neck cosmetic effect was assessed by postoperative recovery time of the suprasternal fossa and subjective satisfaction questionnaire. Each variable was measured preoperatively, at 2 weeks, 3 months and 6 months after operation. RESULTS: In both groups, the subjective voice, sensory and swallowing symptoms deteriorated at 2 weeks and improved at 3 months postoperatively. Indicators of VHI, SIS and 3 oz water swallow test returned to the preoperative level at 6 months after operation. In the subfascial group, SIS was significantly better than that of the subplatysmal group (p = 0.005) at 2 weeks after operation. The recovery time of the suprasternal fossa in the subfascial group was delayed (p = 0.158), compared with the subplatysmal group. CONCLUSION: The subfascial approach may have certain advantages in swallowing symptoms basing on the swallowing impairment test. However, the subplatysmal approach and the subfascial approach may have the same cosmetic effect.

Polyamine effects on protein disulfide isomerase expression and implications for hypersalinity stress in the marine alga Ulva lactuca Linnaeus(1).

Full-length protein disulfide isomerase (UfPDI) cDNA was cloned from the intertidal macroalga Ulva lactuca Linnaeus. Modulation of UfPDI expression by stresses and polyamines (PA) was studied. UfPDI transcription and enzyme activity were increased by hypersalinity (90) or high light illumination (1,200 µmol photons · m(-2)  · s(-1) ), decreased by the addition of 100 µM CuSO4 . An exposure to a salinity of 90 decreased PA contents. Treating with PA biosynthetic inhibitors, D-arginine (D-Arg) or α-methyl ornithine (α-MO), led to a further decrease and also inhibited UfPDI expression and recovery of the growth rate. These results suggest that PAs are required to activate UfPDI expression with hypersalinity, even PA contents are decreased at a salinity of 90. The induction of UfPDI expression by hypersalinity of 90 and tolerance to hypersalinity could be enhanced if internal PA contents rise. Sung et al. (2011b) showed that PA contents could be increased by pretreating with putrescine (Put, 1 mM), spermidine (Spd, 1 mM), or spermine (Spm, 1 mM) at a salinity of 30. Therefore, PA pretreatment effect on UfPDI expression was examined. Pretreatment with Spd and Spm, but not with Put, enhanced UfPDI expression after transferred to a salinity of 90 and restored the growth rate. In conclusion, induction of UfPDI expression by Spd or Spm before exposure to hypersaline conditions and continuous up-regulation after hypersalinity exposure are required for the acquisition of hypersalinity tolerance in the intertidal green macroalga U. lactuca.

Cerebellar Purkinje cell neurodegeneration after cardiac arrest: effect of therapeutic hypothermia.

AIMS: The cerebellum is among the brain regions most vulnerable to damage caused by cardiac arrest, and cerebellar Purkinje cell loss may contribute to neurologic dysfunction, including post-hypoxic myoclonus. However, it remains unknown whether cerebellar Purkinje cells are protected by post-cardiac arrest therapeutic hypothermia (TH). Therefore, we examined the effect of post-cardiac arrest TH onset and duration on cerebellar Purkinje cell loss. METHODS: Samples from a previously published study of post-cardiac arrest TH were utilized for the present analysis. Adult male rats subjected to asphyxial cardiac arrest and cardiopulmonary resuscitation were block randomized to normothermia (37.0°C) or TH (33.0°C) initiated 0, 1, 4, or 8h after return of spontaneous circulation (ROSC) and maintained for 24 or 48 h. Cerebella from rats surviving 7 days after ROSC were processed for histology and immunohistochemistry. Purkinje cell density was quantified in Nissl-stained sections of the primary fissure of the cerebellar vermis. RESULTS: With post-cardiac arrest normothermia, Purkinje cell density in the primary fissure was severely reduced compared to sham-injured controls (3.8 ± 1.8 cells mm(-1) vs. 35.9 ± 2.4 cells mm(-1), p<0.001). TH moderately improved Purkinje cell survival in all groups combined (14.0 ± 5.6 cells mm(-1), p<0.001 compared to normothermia). There was no statistical difference in Purkinje cell protection based on TH onset time or duration. CONCLUSION: These results indicate that post-cardiac arrest TH protects selectively vulnerable cerebellar Purkinje cells within a broad therapeutic window. The potential clinical implications for improving Purkinje cell survival require further investigation.

Short-duration treatment with the calpain inhibitor MDL-28170 does not protect axonal transport in an in vivo model of traumatic axonal injury.

Traumatic axonal injury is characterized by early cytoskeletal proteolysis and disruption of axonal transport. Calpain inhibition has been shown to protect axons in rodent models of traumatic brain injury. However, in these models, both white and gray matter are injured, making it difficult to determine if calpain inhibitors are directly protecting injured axons. To address this issue, we used our rat optic nerve stretch model to test the hypothesis that early calpain inhibition directly protects central nervous system (CNS) axons following stretch injury. Rats were given an intravenous bolus of the calpain inhibitor MDL-28170 (30 mg/kg) 30 min prior to unilateral optic nerve stretch, followed by a 15 mg/kg/h intravenous infusion over the next 2.5 h. Immunohistochemical analysis of optic nerves 30 min after stretch injury revealed variable increases of calpain-cleaved α-spectrin that appeared less evident in stretched nerves from drug-treated rats, although this difference was not statistically significant. Retrograde axonal transport measured by Fluorogold® labeling of retinal ganglion cells was significantly impaired after stretch injury. However, there was no difference in the number of Fluorogold-labeled cells in the vehicle vs. drug treatment groups. These results suggest that early short-duration calpain inhibitor therapy with MDL-28170 is not an effective strategy to prevent disruption of axonal transport following isolated axonal stretch injury in the CNS.

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

RATIONALE: Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. OBJECTIVE: This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. MATERIALS AND METHODS: LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. RESULTS: Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. CONCLUSIONS: LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

RNAi targeting micro-calpain increases neuron survival and preserves hippocampal function after global brain ischemia.

The calpain family of cysteine proteases has a well-established causal role in neuronal cell death following acute brain injury. However, the relative contribution of calpain isoforms has not been determined in in vivo models. Identification of the calpain isoform responsible for neuronal injury is particularly important given the differential role of calpain isoforms in normal physiology. This study evaluates the role of m-calpain and micro-calpain in an in vivo model of global brain ischemia. Adeno-associated viral vectors expressing short hairpin RNAs targeting the catalytic subunits of micro- or m-calpain were used to knockdown expression of the targeted isoforms in adult rat hippocampal CA1 pyramidal neurons. Knockdown of micro-calpain, but not m-calpain, prevented calpain activity 72 h after 6-min transient forebrain ischemia, increased long-term survival and protected hippocampal electrophysiological function. These findings represent the first in vivo evidence that reducing expression of an individual calpain isoform can decrease post-ischemic neuronal death and preserve hippocampal function.